Potent hypoglycaemic activity of the aqueous extract of Chamaemelum nobile in normal and streptozotocin-induced diabetic rats

The purpose of this study was to investigate the effect of both a single dose and daily oral administration for 15 days of the aqueous extract of the aerial part of Chamaemelum nobile (C. nobile) at a dose of 20mg/kg body weight on blood glucose concentrations and basal insulin levels in normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of C. nobile aqueous extract reduced blood glucose levels from 6.0 +/- 0.3 mmol/l to 4.9 +/- 0.09 mmol/l (P < 0.05) 6h after administration in normal rats and from 21.1 +/- 1.3 mmol/l to 14.5 +/- 0.9 mmol/l (P < 0.001) in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 6.1 +/- 0.06 mmol/l to 4.6 +/- 0.17 mmol/l (P < 0.01) and from 21.1 +/- 1.31 mmol/l to 13.7 +/- 0.9 mmol/l (P < 0.01) in normal and STZ diabetic rats, respectively, after 15 days of treatment. Basal plasma insulin concentrations remain unchanged after treatment in both normal and STZ diabetic rats so the mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of C. nobile exhibits a significant hypoglycaemic effect in normal and STZ diabetic rats without affecting basal plasma insulin concentrations and support, therefore, its traditional use by the Moroccan population.     

On the mechanism of the hypoglycaemic effect of a plant extract

Summary The efficacy of a hypoglycaemic plant extract, in common use by Kuwaiti diabetic individuals, was evaluated using both streptozotocin-induced diabetic and normal rats. A significant decrease in blood glucose concentration was demonstrated on glucose tolerance tests, as compared to untreated animals. The sum of the fasting, 1 and 2 h blood glucose values, decreased from 18.5±0.72 to 13.6±0.62mmol/l (p < 0.001) and from 58.6±2.83 to 44.5±3.12 mmol/l (p <0.005) in normal and diabetic animals treated for 1 week, respectively. Treatment with the extract was not found to significantly alter insulin levels or intestinal glucose absorption. The mode of action of the hypoglycaemic preparation remains to be elucidated.     

The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and rat islets and HIT-T15 B cells

Summary In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p<0.01) lower and serum insulin levels were significantly (p<0.01) higher in treated diabetic animals (10.4±1.0 mmol/l and 12.8±1.1 U/ml respectively) compared to untreated diabetic controls (17.4±1.7 mmol/l and 8.0±0.7 U/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion.     

Hypoglycemic and hypolipidemic activity of Hibiscus rosa sinensis Linn on streptozotocin–induced diabetic rats

To investigate the hypoglycemic activity of an aqueous extract of the flower of Hibiscus rosa sinensis on blood glucose in normal and streptozotocin (STZ) -induced diabetic rats, serum triglyceride and cholesterol levels and the effect of the flower extract on insulin secretion. Effect of H. rosa sinensis flower extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rats. Glycosylated hemoglobin, serum insulin levels and lipid profile were also determined. Student??s t test was used for statistical analysis. In normal rats, the aqueous extract of the flower of H. rosa sinensis (250 and 500?mg/kg body weight) significantly (P?<?0.001) reduced the blood glucose levels after an oral glucose load from 127.9?±?5.6 to 80.6?±?3.9?mg/dl 2?h after oral administration of the flower extract. It also significantly lowered the blood glucose in STZ diabetic rats from 241.0?±?6.6 to 90.8?±?5.7?mg/dl after 21?days of oral administration of the extract (P?<?0.001). Serum insulin levels were not stimulated in the animals treated with the extract. Glycosylated hemoglobin and serum lipid profiles were significantly lowered by the administration of the extract. From the studies, it can be concluded that the aqueous extract of the flowers of H. rosa sinensis at a dosage of 500?mg/kg/day exhibits significant hypoglycemic and hypolipidemic activities. A marked reduction in glycosylated hemoglobin was also observed while insulin levels did not show any significant change.     

The Acute Effect of Preprandial Exogenous and Endogenous Sulphonylurea-stimulated Insulin Secretion on Postprandial Glucose Excursions in Patients with Type 2 Diabetes

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin responses to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p<0.01), whereas total insulin release was equally improved (78% and 54% vs control; p<0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol × min I^?1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p<0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol × min I^?1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol × min I^?1; p<0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral pre-meal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.     

HbA1c levels are better predicted by prebreakfast than postbreakfast blood glucose self-analyses in type 2 diabetes. Influence of duration of diabetes and mode of treatment

The present study aimed at assessing the capability of both prebreakfast and postbreakfast home blood glucose self-analyses to predict HbA1c in type 2 diabetic individuals and the influence of duration of diabetes or mode of treatment in this regard. Two hundred and twenty-seven type 2 diabetic individuals consecutively attending our diabetes clinic between January 2000 and December 2002 (42.3% placed on oral drugs and 57.7% receiving insulin therapy, either alone or as a combination with oral drugs) were retrospectively selected and three more recent values regarding both home prebreakfast and one-hour postbreakfast blood glucose self-analyses were averaged. Patients were classified by their mode of treatment (submission or not to insulin therapy) and by quartile of duration of diabetes. The correlations of HbA1c levels with either prebreakfast or postbreakfast blood glucose self-analyses were performed in the whole group and in every subset considered. HbA1c values had a stronger correlation with prebreakfast blood glucose self-analyses (r=0.53, p<0.001) than with one-hour postbreakfast home glucose self-analyses (r=0.39, p<0.001). Prebreakfast (but not onehour postbreakfast) blood glucose self-analysis was selected as independently associated to HbA1c levels in a multiple regression analysis performed upon the whole study group as well as in most of the subsets considered. HbA1c values had a stronger correlation with prebreakfast glucose self-analyses in individuals with a shorter duration of diabetes (r=0.71, p<0.001) and not submitted to insulin therapy (r=0.59, p<0.001). Increasing age characterised individuals with the highest postbreakfast glucose excursions (one-way ANOVA, p<0.01). These data suggest that prebreakfast blood glucose self-analyses are more closely related to HbA1c levels than one-hour postbreakfast blood glucose self-analyses in most of the clinical spectrum of type 2 diabetes mellitus.     

Insulin Infusion Normalizes Cardiovascular Responses and Plasma Noradrenaline after Oral Glucose in Type 1 (Insulin-dependent) Diabetes

ABSTRACT. We examined whether the abnormal regulation of the cardiovascular system and plasma noradrenaline observed after oral glucose in insulin-dependent diabetic patients could be normalized by intravenous infusion of insulin. Eight patients with type 1 (insulin-dependent) diabetes were examined after an oral glucose load with and without simultaneous infusion of insulin. Insulin infusion increased plasma insulin from 0.07 to 0.31 nmol/1. In the control experiment (glucose only), mean heart rate and mean arterial systolic blood pressure remained unchanged and plasma noradrenaline (NA) decreased (p < 0.05). After oral glucose plus intravenous insulin, mean heart rate increased by 11 % and mean systolic blood pressure by 5 % (p < 0.05, p < 0.01), whereas plasma NA did not change significantly. The present study indicates that physiologic increments in plasma insulin concentration are of importance in the regulation of the cardiovascular system and plasma NA following an oral glucose load.     

Effects of Gmelina arborea extract on experimentally induced diabetes

ObjectiveTo study the effects of aqueous extract of Gmelina arborea bark on normoglycemic levels and streptozotocin (STZ) induced diabetes in rats.MethodsAfter single administration of the aqueous extract, plasma glucose level was determined up to 6 h. In subacute study, the aqueous extract was administered for 28 d and plasma glucose level was determined weekly. The diabetes was induced in rats by the intraperitoneal injection of STZ at a dose of 55 mg/kg body weight. The diabetic animals were divided into four groups containing six in each: Group I diabetic control, Group II and III treated with the aqueous extract respectively at a dose of 250 and 500 mg/kg body weight once daily and Group IV treated with glibenclamide at a dose of 0.6 mg/kg body weight once daily. In acute study, the aqueous extract and glibenclamide were administered orally to rats. Plasma glucose levels were determined at 30, 60, 120, 240 and 360 min after the administration of the test samples. To study subacute effects, test samples (the aqueous extract and glibenclamide) were administered for 28 d consecutively. The effects of each test sample on plasma glucose level, body weight as well as food and water intake were also monitored weekly. The oral glucose tolerance test and biochemical indicators were estimated on day 28.ResultsThe aqueous extract did not significantly decrease the plasma glucose level in the normoglycemic rats as shown by the acute and subacute assays. However, after oral administration of the aqueous extract, the plasma glucose level was significantly (P<0.001) decreased in the diabetic rats in the acute study. The long-term administration of the aqueous extract significantly (P<0.001) reduced plasma glucose levels of the diabetic rats. Additionally, the aqueous extract also reduced loss of body weight and significantly decreased food and water intake in the diabetic animals. Nevertheless, no effects on biochemical indicators were observed at the selected doses.ConclusionsThe aqueous extract of Gmelina arborea bark had antihyperglycemic activity against STZ induced diabetes in rats, after single and subacute oral administration. Moreover, it did not show significant glucose lowering effect in normoglycemic rats.     

Comparison of portal and peripheral insulin delivery on carbohydrate metabolism in streptozotocin-diabetic rats

Summary Severely diabetic rats (150 mg streptozotocin/kg) were transplanted with fetal pancreatic islets: (a) under the kidney capsule to model peripheral insulin delivery, and (b) into the splenic pulp to model portal delivery. Long-term normoglycaemia, normal weight gain and normal peripheral insulin levels were achieved in both groups of transplanted animals. In both groups, 24-h fasted blood lactate, pyruvate and alanine were identical to those observed in sham-operated control animals. Blood glucose and plasma insulin responses to 300 mg oral glucose 8 weeks after transplantation were the same as in control animals. Hepatic glycogen concentration was, however, lower in fed rats with islets beneath the kidney capsule compared with control rats (p<0.01), suggesting inadequate hepatic insulinisation in the fed state with peripheral insulin delivery. Muscle glycogen was the same as in controls. Glucose turnover and glucose carbon recycling were not significantly different from results in normal control and splenic pulp islet-transplanted animals. The findings indicate that consistent normoglycaemia, normal glucose flux and normalisation of blood intermediary metabolites can be achieved in the rat with peripheral insulin delivery without associated hyperinsulinaemia.     

Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin and hepatic enzymes of glucose metabolism in hyperglycaemic rats

AIM: The present study was designed to investigate the effect of diasulin, a polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in this study. The rats were divided into seven groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1: normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10 g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of glibenclamide (600 micro g/kg of body weight). The treatment was given for 30 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with diasulin resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in plasma insulin and total haemoglobin and a significant improvement in glucose tolerance. Diasulin also resulted in a significant reduction in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity was significantly increased in alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that diasulin, a polyherbal drug, controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible, because it regulates the activities of hepatic glucose metabolic enzymes.     

The effect of oral synthetic protease inhibitor (FOY 305) on endocrine pancreas and carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats

The effect of long-term oral synthetic protease inhibitor (FOY 305) administration on fasting blood sugar (FBS), body weight, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, hepatic enzyme activities, and plasma lipids in normal and streptozotocin (STZ)-induced diabetic rats was studied. Normal rats treated with oral FOY 305 for 9 weeks were found to have pancreatic hypertrophy and decreased body weight gain as compared with the untreated normal controls. FBS, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, and plasma lipids were uninfluenced in FOY 305 treated normal rats. STZ-induced diabetic rats treated with oral FOY 305 were found to have decreased FBS for 5 weeks after the beginning of FOY 305 administration as compared with the untreated diabetic controls, whereas at the 7th and 9th week after treatment there was no difference in FBS between FOY 305 treated and untreated diabetic rats. In the metabolic balance observed at the 4th week after treatment, a slight improvement of the diabetic state was found in FOY 305 treated diabetic rats. There was no apparent difference in the blood sugar curve and insulin response following oral glucose load between diabetic rats treated for 7 weeks and untreated diabetic rats. All the rats were sacrificed after 9 weeks of treatment. Diabetic rats treated with oral FOY 305 for 9 weeks showed pancreatic hypertrophy and decreased plasma glucagon level and decreased pancreatic glucagon content as compared with the untreated diabetic controls, whereas there was no difference in body weight, plasma insulin level and pancreatic insulin content between FOY 305 treated and untreated diabetic rats. Furthermore, oral FOY 305 treatment improved hyperlipidemia in STZ-induced diabetic rats and also significantly improved the hepatic pyruvate kinase and phosphoenlpyruvate carboxykinase activities of diabetic rats. These improvements might partly be due to a decreased pancreatic content and secretion of glucagon and/or a direct action of the synthetic PI, FOY 305 to tissues.     

小檗碱对实验大鼠糖脂代谢的影响

目的探讨小檗碱对实验大鼠胰岛素敏感性和血糖血脂的影响。方法实验大鼠分7组：普食对照组和小檗碱治疗组，高脂对照组和小檗碱治疗组，高脂饮食与极小剂量链脲佐菌素(STZ)诱导的糖尿病对照组，糖尿病小檗碱治疗组和二甲双胍治疗组。疗程为5周。以糖耐量试验评估胰岛功能，以胰岛素耐量试验中的降糖率检测胰岛素敏感性。结果(1)小檗碱使糖尿病鼠的降糖率升高48％，疗效较二甲双胍为好；小檗碱使高脂鼠的胰岛素敏感因子升高78％，延缓了普食鼠降糖率的下降；(2)小檗碱显著降低了高脂大鼠的空腹血糖和负荷血糖；(3)小檗碱使普食鼠、高脂鼠和糖尿病鼠的血清游离脂肪酸分别下调14％、24％和20％，使高脂鼠的血清甘油三酯降低57％。结论小檗碱有显著的胰岛素增敏和降低血清游离脂肪酸的作用，并能降低高脂大鼠的血糖。     

Effect of human umbilical cord blood CD34+ progenitor cells transplantation in diabetic mice

Shortage of donor organs spurs research into alternative means of generating β cells. Stem cells might represent a potential source of tissues for cell therapy protocols, and diabetes is a candidate disease that may benefit from cell replacement protocols. We examined the effect of transplanted human umbilical cord blood CD34+ cells on some detailed parameters in streptozotocin- (STZ) induced diabetic mice. An experimental study was conducted in the departments of clinical pathology, physiology and pathology of Faculty of Medicine, Suez Canal University. Thirty male albino mice 8–12 weeks were included and subdivided into 3 groups, first group served as normal control group, second group as diabetic control after induction of diabetes with STZ and third group treated diabetic mice by injection of positively selected CD34 progenitor cells from human umbilical cord blood (HUCB) with a dose of one million cells/mouse. Blood glucose and serum insulin were measured at specific time interval and immunohistochemical (IHC) analysis and histopathology on pancreas were conduced. Data were analyzed using chi square between groups. Intravenous injection of CD34+ cells caused significant improvement in blood glucose level (277.9?±?102.5 mg/dl in treated group vs 530.3?±?99 mg/dl in untreated group, p?<?0.01). Blood level of mouse insulin was higher in the treated group as compared with untreated diabetic mice (0.77?±?0.2 ng/ml in treated group versus 0.26?±?0.09 in untreated group, p?<?0.001). IHC analysis for detection of human insulin producing cells in pancreas of treated mice revealed that 33.3% positive cellular staining and 55.6% positive sinusoidal staining were detected. In conclusion, Transplantation of HUCB-CD34+ cells appear to be a modality of stem cell therapy in diabetes mellitus.     

Effect of cogent db,a herbal drug,on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes

Aims: The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats.
Methods: Male Wistar rats body weight of 180–200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 µg/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals.
Results: Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats.
Conclusions: The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.     

Hydroethanolic extract of Smallanthus sonchifolius leaves improves hyperglycemia of streptozotocin induced neonatal diabetic rats

Objective: To evaluate the effect of hydroethanolic extract of yacon on the hyperglycemia induced by streptozotocin(STZ) in neonatal rats. Methods: Wistar rats aged two days old received an intraperitoneal injection of STZ(160 mg/kg); after seven weeks, glycosuria was determined and animals with glucose levels above 250 mg/d L were included in the study. Groups of diabetic and non-diabetic rats were treated orally with yacon extract at a dose of 400 mg/kg/d for 14 d. Tests were made for phytochemical characterization, glucose tolerance and toxicity. Results: The results showed that treatment with the extract reduced the glucose levels of fed diabetic rats and did not change the glucose levels of fasting diabetic and normal rats. Additionally, also it was observed that treatment with the extract reduced blood glucose levels of diabetic rats during the oral and intravenous glucose tolerance tests. There was no change in body weight, liver enzymes or mortality with yacon extract treatment. The phytochemical screening revealed the presence of caffeic acid, chlorogenic acid, ferulic acid and gallic acid. Conclusions: The data suggest that yacon extract reduces hyperglycemia, possibly by improving insulin sensibility through its phytochemicals constituents(phenolic compounds).     

Glucose tolerance and insulin secretion in children of mothers with pregestational IDDM or gestational diabetes

Summary The offspring of mothers with diabetes mellitus during pregnancy are presumed to develop altered glucose homeostasis. We analysed metabolic parameters at birth and glucose tolerance and insulin secretion during oral glucose tolerance tests at 1–9 years of age in 129 children born to mothers with pregestational insulin-dependent diabetes (IDDM) and 69 infants of gestational diabetic mothers. Newborns of IDDM mothers displayed higher insulin (p < 0.001), glucose (p < 0.05), and insulin/glucose ratios (p < 0.002) than newborns of gestational diabetic mothers. During childhood, frequencies of impaired glucose tolerance (IGT) rose in infants of IDDM mothers from 9.4 % at 1–4 years to 17.4 % at 5–9 years of age, while in children of gestational diabetic mothers an increase from 11.1 % up to 20.0 % was observed. Offspring of gestational diabetic mothers displayed higher stimulated blood glucose (p < 0.025) than infants of IDDM mothers, while children of IDDM mothers showed higher stimulated insulin (p < 0.025), accompanied by increased fasting and stimulated insulin/glucose ratios (p < 0.05 and p < 0.02, respectively). Stimulated insulin in childhood was positively correlated to insulin at birth (p < 0.05). Furthermore, insulin/glucose ratio in childhood showed a positive correlation to insulin (p < 0.01) and insulin/glucose ratio at birth (p < 0.005). In conclusion, a pathogenetic role of fetal and neonatal hyperinsulinism for the development of IGT in both groups of infants of diabetic mothers is suggested, in particular for early induction of insulin resistance in the offspring of mothers with pregestational IDDM. [Diabetologia (1997) 40: 1097–1100] Received: 24 February 1997 and in revised form: 7 May 1997     

Glycemic control with an artificial pancreas improves insulin responses to both oral and I.V. Glucose in nonobese noninsulin-dependent diabetic subjects

Summary Insulin secretory responses to both oral and intravenous glucose were investigated in 12 nonobese noninsulin-dependent diabetic subjects before and after strict metabolic control of blood glucose levels without weight loss. Glycemic control was achieved by applying an artificial pancreas to all diabetics for 2 or 3 days, which led to restoration of normal fasting blood glucose levels and to significant reduction of fasting plasma insulin (p<0.01) and C-peptide (p<0.05) levels. Initially, the insulin response to oral glucose was weak and delayed, but increased significantly after treatment (p<0.01), although none of the diabetic subjects achieved completely normal glucose tolerance. The i.v. glucose tolerance test (0.33 g/kg) revealed that all diabetics lacked acute insulin response in the basal state with low glucose disappearance rates (0.37±0.07 %/min). After 48h of normoglycemia, these figures did not change significantly, although the insulinogenic index (insulin area/glucose area) was significantly increased (p<0.05). A marked increase in both phases of insulin secretion was evident when a larger intravenous glucose pulse (0.66 g/kg) was used in some diabetics in order to raise the blood glucose concentrations of the post-treatment test to those of the pre-treatment test. In absolute terms, the insulin responses of the post-treatment tests were not significantly different from those of sex, age- and weightmatched control subjects, but were signficantly lower if related to the corresponding plasma glucose responses (insulinogenic index lower than that of controls). These studies in nonobese noninsulin-dependent diabetic subjects indicate that glycemic control with an artificial pancreas improves insulin response to glucose, suggesting that chronic hyperglycemia may stress the impaired B-cell secretory capacity of diabetes.     

Gastric inhibitory polypeptide and the entero-insular axis in streptozotocin diabetic mice

The function of the entero-insular axis and abnormalities of circulating gastric inhibitory polypeptide (GIP) were examined in mice for 40 days after induction of streptozotocin diabetes. Compared with untreated controls, streptozotocin diabetic mice exhibited marked hyperglycaemia and hypoinsulinaemia, with impaired body weight gain, lipoatrophy, hyperphagia, intestinal hypertrophy, polydipsia and renal hypertrophy. Plasma GIP concentrations were elevated in fed but not fasted streptozotocin diabetic mice, and oral fat evoked a greater GIP response than control mice. In spite of marked hyperglycaemia, fat-stimulated GIP release did not raise plasma insulin in streptozotocin diabetic mice. Neither oral nor intraperitoneal glucose produced a significant insulin response in streptozotocin diabetic mice, although oral glucose resulted in a smaller change in glycaemia. The results indicate that streptozotocin diabetes in mice is associated with ineffectiveness of the entero-insular axis, despite elevated GIP concentrations, which are probably mediated through hyperphagia and defective feedback inhibition by insulin on intestinal K cells.     

Insulin secretory response to oral glucose load,diabetic microangiopathy and diabetic control: A study in non-insulin dependent diabetics

To study the importance of the residual insulin secretion for the degree of diabetic control and for the development of microangiopathy 55 patients with nonpinsulin-dependent diabetes mellitus (NIDDM) were studied. A 1 hr oral glucose tolerance test was performed at diagnosis and 5–10 yr later. At diagnosis all patients were free of microangiopathy, at ressessment 24 patients had evidence of microangiopathy, i.e. retinopathy, neuropathy or nephropathy, alone or in combination. The glucose induced increments of insulin levels (ΔIRI) at reassessment correlated inversely with the degree of diabetic control, measured by Haemoglobin A₁ (r = ?0.466, p < 0.01), and with the mean fasting blood glucose throughout the follow up period (r = ?0.491, p < 0.01). ΔIRI at diagnosis was similar in patients with and without microangiopathy, and at reassessment, although lower in the microangiopathy group (11.2 ± 2.1 vs. 16.4 ± 2.1 μU/ml, p < 0.1). The difference between the 2 groups did not reach statistical significance. When patients were separated into those treated with diet alone and those treated with oral antidiabetic agents, ΔIRI at reassessment was significantly lower in patients on oral agents (10.5 ± 1.9 vs. 17.2 ± 2.2 μU ml, p < 0.01), but the prevalence of microangiopathy was not different between 2 groups (37% and 52%, respectively). These findings show that in patients with NIDDM the residual beta cell function is important for the degree of diabetic control, but a direct relationship between the degree of insulin deficiency and the presence of diabetic microangiopathy is not established.     

Antihyperglycemic activity, antihyperlipedemic activity, haematological effects and histopathological analysis of Sapindus mukorossi Gaerten fruits in streptozotocin induced diabetic rats

ObjectiveTo investigate the antihyperglycemic and antihyperlipidemic properties of hydroalcoholic extract of fruits of Sapindus mukorossi Gaerten and its beneficial effect on haematological parameters with histopathological analysis in streptozotocin induced diabetic rats.MethodsSapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and standard drug glybenclamide (0.5 mg/kg body weight) were administered to diabetic rats. Effect of extract on hyperglycemia, hyperlipidemia and hematological parameters was studied in diabetic rats. Histopathological changes in diabetic rat pancreas were also observed after extract and glybenclamide treatment.ResultsDaily oral administration of Sapindus mukorossi fruits extract (250 and 500 mg/kg body weight) and glybenclamide for 20 days showed beneficial effects on blood glucose level (P<0.01) and lipid level. The extract has a favorable effect on the histopathological changes of the pancreas in streptozotocin induced diabetes.ConclusionThese findings reveal that the hydroalcoholic extract of Sapindus mukorossi fruits extract possesses antihyperglycemic and antihyperlipidemic properties. In addition, the extract can prevent various complications of diabetes and improve some haematological parameters.