Hormonal effects on gluconeogenesis from (U-14C)glutamate in rainbow trout (Salmo gairdneri)

Blood glucose was significantly decreased by insulin (4 I.U./kg). Glucagon (1 mg/kg) and Cortisol (5 mg/kg) administration produced a significant hyperglycaemia. Insulin administration did not modify liver glycogen levels. Glucagon showed a marked liver glycogen mobilization. Cortisol stimulated liver glycogen deposition. Insulin and Glucagon showed a significant inverse effect on gluconeogenesis from (U-14C)glutamate, decreasing and increasing 14C-glucose formation respectively. Hormonal treatments did not influence the very low levels of incorporation of (U-14C)glutamate into liver and muscle glycogen.     

Effect of bromocriptine on lipid plasma levels in rats

Results show that bromocriptine induced marked alterations in plasma levels of cholesterol and lipids in response to acute and chronic administrations in rats. Two hours after an I.P. dose of 10 mg/kg, bromocriptine mesylate caused significant reductions in plasma levels of total high density lipoprotein (HDL) and high density lipoprotein cholesterol (HDL cholesterol). At a dose of 20 mg/kg, bromocriptine mesylate induced significant elevations in plasma levels of total cholesterol, total HDL, HDL cholesterol, total low density lipoproteins (LDL), and low density lipoprotein cholesterol (LDL cholesterol). Injected at a dose of 4 or 10 mg/kg daily for 14 consecutive days, bromocriptine mesylate caused significant increases in plasma levels of total cholesterol, LDL cholesterol and total LDL whereas the levels of HDL cholesterol, total HDL triglycerides (TG) were reduced. At a dose of 20 mg/kg all parameters were significantly increased. Marked hyperglycaemia was noticed in response to doses of 10, 15 and 20 mg/kg injected daily for 14 consecutive days or 2 hrs after a single administration of 15 mg/kg. Plasma insulin activity was reduced 2 hours after injection of bromocriptine at a dose of 15 mg/kg Likewise, a significant reduction in plasma insulin activity was observed in response to daily I.P. injections of bromocriptine at a dose of 15 mg/kg. Hyperglycaemic and hypoinsulinaemic effects of bromocriptine (acute and chronic) were markedly decreased when sulpiride, a dopaminergic D2 antagonist, was injected at an I.P. dose of 10 mg/kg before bromocriptine. Plasma ACTH activity was significantly increased in response to bromocriptine (15 mg/kg I.P.) in acute and chronic experiments. This effect was markedly diminished when sulpiride was injected prior to bromocriptine. In conclusion, bromocriptine induced marked elevations in plasma levels of total cholesterol and lipids which are likely to be related to hyperglycaemic and hypoinsulinaemic effects.     

Hepatotoxicity induced by diethylnitrosamine causes no significant disturbances of systemic glucose homeostasis in rats

In rats, a moderately hepatotoxic single dose of diethylnitrosamine (DEN) 100 mg/kg causing depletion of liver glycogen, elevation of aspartate aminotransferase and decreased liver uptake of 3-O-methylglucose, resulted in substantial changes in insulin and glucagon balance. Two days after DEN, insulin binding to liver membranes and insulin removal by the liver were sharply reduced whereas its binding to muscle and adipocyte membranes remained unaltered. Serum insulin (random and after an overnight fast) remained normal. Intravenous (I.V.) insulin (10 U/kg) caused the usual degree of hypoglycemia that, however, lasted longer than in the control animals. Removal of glucagon by liver was also depressed in spite of its normal binding to hepatocytes, and peripheral serum glucagon was increased three-fold. I.V. glucagon (40 micrograms/kg) resulted in a blunted response of plasma glucose. I.V. glucose tolerance test (1 g/kg) remained normal in spite of the insulin increase to a level twice as high as in the controls, and in spite of nonsuppressed glucagon. These changes were still present after 1-3 months, but disappeared by 6 months. The results demonstrate remarkable ability of homeostatic mechanisms to preserve normal plasma glucose and glucose tolerance in spite of dramatic changes in insulin and glucagon.     

Sensitivity and responsiveness of glucose output to insulin in isolated perfused liver from dexamethasone-treated rats

To elucidate insulin action on hepatic glucose output (glycogenolysis) in the state exposed to an excess glucocorticoid, the fed rat liver was isolated and cyclically perfused with a medium containing 5 mM glucose and various concentrations of insulin. The rat was subcutaneously injected with 1 mg/kg of dexamethasone (Dex) for 7 days. Dex-treated rats showed marked increases of serum insulin and plasma glucose level compared with those in control rats. Hepatic glycogen contents in Dex group were markedly increased compared with those in control (115 +/- 5 and 28 +/- 4 mg/g, respectively). Insulin extraction rate in the perfused liver was not different between control and Dex group. Perfusate glucose level after 60 min perfusion was much higher in the Dex-treated rat liver than that of the control at 0 microU/ml insulin (34.5 +/- 2.5 vs 23.0 +/- 2.0 mM, P less than 0.01), and reduced to the nadir level (19.0 +/- 3.0 and 13.0 +/- 1.5 mM, respectively) at 100 microU/ml insulin in both groups, i.e., the decreasing rate in perfusate glucose level was not different between Dex and control group (43% and 44%, respectively). These results suggest that Dex-treatment augments hepatic glucose output, but does not affect the sensitivity and responsiveness of that to insulin.     

Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice

Diabetes mellitus (DM) often leads to disability from vascular complications and neurological complications. Tinospora crispa has been widely used in Asia and Africa as a remedy for diabetes and other diseases. In this study, we investigated the hypoglycemic actions of borapetoside C isolated from T. crispa, and the mechanisms underlying its actions. Acute treatment with borapetoside C (5mg/kg, i.p.) attenuated the elevated plasma glucose induced by oral glucose in normal and type 2 DM (T2DM) mice. Compared to the effect of injected insulin (0.5 IU/kg), borapetoside C caused a more prominent increase of glycogen content in skeletal muscle of T2DM mice, but a less increase in type 1 DM (T1DM) mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, i.p.) plus insulin enhanced insulin-induced lowering of the plasma glucose level and insulin-induced increase of muscle glycogen content. Continuous treatment with 5mg/kg borapetoside C (twice daily) for 7 days increased phosphorylation of insulin receptor (IR) and protein kinase B (Akt) as well as the expression of glucose transporter-2 (GLUT2) in T1DM mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, twice daily) plus insulin for 7 days enhanced insulin-induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice. This study proved that borapetoside C can increase glucose utilization, delayed the development of insulin resistance and enhanced insulin sensitivity. The activation of IR-Akt-GLUT2 expression and the enhancement of insulin sensitivity may contribute to the hypoglycemic action of borapetoside C in diabetic mice.     

Effect of salvipholin on the carbohydrate and lipid metabolism in the rat liver in alloxan diabetes]

Peroral administration of salvipholin in a dose of 50 mg/kg to intact male rats (the body weight 180-220 g) had a positive effect on the carbohydrate-lipid metabolism in the liver and blood serum of animals. Administration of the same dose to rats with alloxan diabetes induced a significant decrease in the content of glucose, free fat acids, triglycerides and lysophospholipids of the liver and blood serum. The level of these components has sharply increased after subcutaneous alloxan administration in a dose of 150 mg/kg, the content of glycogen and pyruvic acid being normalized and insulin deficiency removed. These changes are closely related to salvipholin-promoted restoration of phospholipid spectra of the blood serum and liver of experimental animals disturbed under conditions of insulin deficiency. The possible mechanism of the salvipholin action is analyzed.     

Possible effect of bromocriptine on the insulin receptor

The administration of 0.00011 mg/g weight/day of bromocriptine (CB154) for 7 days to Wistar rats, improved the peripheral glucose uptake without significant changes in plasma insulin level, during the intravenous glucose tolerance test (0.33 g/kg). The mode of the bromocriptine action on binding of 125I insulin to erythrocyte insulin receptors has been evaluated. The total number of sites was greater with bromocriptine (513.1 +/- 124.1 pM/1,CB154 815.6 +/- 107.9 pM/l) (p less than 0.01). The high affinity/low capacity compound of insulin receptor, in CB154 rats (51.8 +/- 16.8 pM/l) was higher than in normal rats (18.3 +/- 8.9 pM/l) (p less than 0.005). Additional studies indicated that CB154 had no effect on the rate of association and dissociation of 125I insulin from rats erythrocyte insulin receptors. The degradation of insulin or the erythrocyte receptor sites do not change, after the treatment with CB154.     

Ameliorating effect and potential mechanism of Rehmannia glutinosa oligosaccharides on the impaired glucose metabolism in chronic stress rats fed with high-fat diet

The aim of this study was to determine whether the Rehmannia glutinosa oligosaccharides (ROS) ameliorate the impaired glucose metabolism and the potential mechanism in chronic stress rats fed with high-fat diet. The rats were fed by a high-fat diet and simultaneously stimulated by chronic stress over 5 weeks. Body weight, fasting plasma glucose, intraperitoneal glucose tolerance test (IPGTT), plasma lipids, gluconeogenesis test (GGT), glycogen content, and corticosterone, insulin and leptin levels were measured. The results showed that ROS administration (100, 200 mg/kg, i.g.) for 5 weeks exerted the effects of increasing the organ weights of thymus and spleen, lowering the fasting plasma glucose level, improving impaired glucose tolerance, increasing the contents of liver and muscle glycogen, decreasing the gluconeogenesis ability, plasma-free fatty acid's level, as well as plasma triglyceride and total cholesterol levels in chronic stress and high-fat fed rats, especially in the group of 200 mg/kg; while the plasma corticosterone level was decreased, and plasma leptin level was increased. These results suggest that ROS exert an ameliorating effect of impaired glucose metabolism in chronic stress rats fed with high-fat diet, and the potential mechanism may be mediated through rebuilding the glucose homeostasis in the neuroendocrine immuno-modulation (NIM) network through multilinks and multitargets.     

Hypoglycemic activity of Swertia chirayita (Roxb ex Flem) Karst

Hexane fraction of S. chirayita (250 mg/kg body wt.) induced significant fall in blood sugar and significant increase in plasma IRI simultaneously after single oral administration without influencing liver glycogen concentration in albino rats. On the other hand, daily administration for 28 days resulted in significant lowering of blood sugar and increase in plasma IRI along with a significant rise in liver glycogen. Intestinal absorption of glucose was not inhibited by hexane fraction. It is suggested that hexane fraction of S. chirayita possibly acts through its insulin releasing effect.     

Short-term insulin infused through the portal vein enhances liver gluconeogenesis and glycogenesis from [3-14C]pyruvate in the starved rat

Insulin infusion through the portal vein immediately after a pulse of [3-14C]pyruvate in 24 hr starved rats enhanced the appearance of [14C]glucose at 2, 5 and 10 min and glucose specific activity at 1, 2 and 20 min in blood collected from the cava vein at the level of the suprahepatic veins. Insulin infusion for 5 min decreased liver pyruvate concentration and enhanced both liver and plasma lactate/pyruvate ratio, and it decreased the plasma concentration of all amino acids. When insulin was infused together with glucose, [14C]glucose levels and glucose specific activity decreased in blood but there was a marked increase in liver [14C]glycogen, glycogen specific activity and glycogen concentration, and an increase in liver lactate/pyruvate ratio. The effect of insulin plus glucose infusion on plasma amino acids concentration was smaller than that found with insulin alone. It is proposed that insulin effect enhancing liver gluconeogenesis is secondary to its effect either enhancing liver glycolysis which modifies the liver's cytoplasmic oxidoreduction state to its more reduced form, increasing liver amino acids consumption or both. In the presence of glucose, products of gluconeogenesis enhanced by insulin are diverted into glycogen synthesis rather than circulating glucose. This together with results of the preceding paper (Soley et al., 1985), indicates that glucose enhances liver glycogen synthesis from C3 units in the starved rat, the process being further enhanced in the presence of insulin.     

Acute peripheral but not central administration of olanzapine induces hyperglycemia associated with hepatic and extra-hepatic insulin resistance

Atypical antipsychotic drugs such as Olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying the metabolic side-effects of these centrally acting drugs are still unknown to a large extent. We compared the effects of peripheral (intragastric; 3 mg/kg/h) versus central (intracerebroventricular; 30 μg/kg/h) administration of Olanzapine on glucose metabolism using the stable isotope dilution technique (Experiment 1) in combination with low and high hyperinsulinemic-euglycemic clamps (Experiments 2 and 3), in order to evaluate hepatic and extra-hepatic insulin sensitivity, in adult male Wistar rats. Blood glucose, plasma corticosterone and insulin levels were measured alongside endogenous glucose production and glucose disappearance. Livers were harvested to determine glycogen content. Under basal conditions peripheral administration of Olanzapine induced pronounced hyperglycemia without a significant increase in hepatic glucose production (Experiment 1). The clamp experiments revealed a clear insulin resistance both at hepatic (Experiment 2) and extra-hepatic levels (Experiment 3). The induction of insulin resistance in Experiments 2 and 3 was supported by decreased hepatic glycogen stores in Olanzapine-treated rats. Central administration of Olanzapine, however, did not result in any significant changes in blood glucose, plasma insulin or corticosterone concentrations nor in glucose production. In conclusion, acute intragastric administration of Olanzapine leads to hyperglycemia and insulin resistance in male rats. The metabolic side-effects of Olanzapine appear to be mediated primarily via a peripheral mechanism, and not to have a central origin.     

Effect of corticosteroids on carbohydrate metabolism in Bufo melanostictus (Schneider)

A single injection of corticosterone (1 or 5 micrograms/50 g body weight) produced a significant elevation in plasma glucose, liver and muscle glycogen contents of B. melanostictus. Single but identical doses of aldosterone had no effect on plasma glucose concentration. Liver and muscle glycogen contents were however significantly augmented. Administration of 1 or 5 micrograms corticosterone and 1 microgram or 200 ng aldosterone/50 g body weight, for 15 days, caused no change in plasma glucose concentration. In all the groups receiving corticosterone or aldosterone for 15 days, liver and muscle glycogen contents significantly increased. The magnitude of increase in liver and muscle glycogen by aldosterone was marginally greater than that by corticosterone. The results suggest that both the corticosteroids may be gluconeogenic in B. melanostictus.     

Panax ginseng improves glucose metabolism in streptozotocin-induced diabetic rats through 5′ adenosine monophosphate kinase up-regulation

5′ AMP-activated protein kinase (AMPK), insulin receptors and transporters are distorted in diabetes mellitus. In this study, the effect of Panax ginseng was assessed on glucose manipulating enzymes activities and gene expression of AMPK, IRA and GLUT2 in streptozotocin-induced diabetic male rats. Forty male albino rats were randomly divided to four groups 10 rats of each, group I, normal control group (received saline orally); group II, normal rats received 200 mg/kg of Panax ginseng orally; group III, Streptozotocin (STZ) –induced diabetic rats and group IV, STZ-induced diabetic rats received 200 mg/kg of Panax ginseng orally. The duration of experiment was 30 days. Results showed the ability of Panax ginseng to induce a significant decrease in the blood glucose and increase in the serum insulin levels, hepatic glucokinase (GK), and glycogen synthase (GS) activities with a modulation of lipid profile besides high expression levels of AMPK, insulin receptor A (IRA), glucose transporting protein-2 (GLUT-2) in liver of diabetic rats. In conclusion, the obtained results point to the ability of Panax ginseng to improve the glucose metabolism in diabetic models.     

Interaction between diazepam and oral antidiabetic agents on serum glucose,insulin and chromium levels in rats

This study was undertaken to investigate the effect of diazepam in the presence and absence of glibenclamide, metformin or their combination on serum levels of glucose, insulin and chromium in rats. Results indicated that diazepam (10 mg/kg i.p.) induced marked hyperglycaemic effects in hyperglycaemic rats. This effect was associated with significant reductions in serum chromium levels and insignificant reduction in serum insulin levels. Diazepam-induced hyperglycaemia was counter-acted by concurrent administration of glibenclamide (5 mg/kg orally), metformin (500 mg/kg orally) or their combination. The effect of diazepam on serum chromium level was counteracted partially by administration of glibenclamide and augmented in the presence of metformin or its combination with glibenclamide. It is concluded that the diazepam-induced hyperglycaemia, as well as the hypoglycaemic effect of glibenclamide, might be related to changes in serum chromium levels.     

Biochemical study of the anti-diabetic action of the Egyptian plants Fenugreek and Balanites

Fenugreek and Balanites are two plants commonly used in Egyptian folk medicine as hypoglycemic agents. In the present study, the effects of 21 days oral administration of Fenugreek seed and Balanites fruit extracts (1.5 g/kg bw) on the liver and kidney glycogen content and on some key liver enzymes of carbohydrate metabolism in STZ-diabetic rats were studied. In addition, the effects of these two plant extracts on the intestinal α-amylase activity in vitro and starch digestion and absorption in vivo were also examined. Results indicated that single injection of STZ (50 mg/kg bw) caused 5-folds increase in the blood glucose level, 80% reduction in serum insulin level, 58% decrease in liver glycogen and 7-folds increase in kidney glycogen content as compared to the normal levels. The activity of glucose-6-phosphatase was markedly increased, whereas, the activities of both glucose-6-phosphate dehydrogenase and phospho-fructokinase were significantly decreased in the diabetic rat liver. Administration of Fenugreek extract to STZ-diabetic rats reduced blood glucose level by 58%, restored liver glycogen content and significantly decreased kidney glycogen as well as liver glucose-6-phosphatase activity. Meanwhile, Balanites extract reduced blood glucose level by 24% and significantly decreased liver glucose-6-phosphatase activity in diabetic rats. On the other hand, our results demonstrated that both the Fenugreek and Balanites extracts were able to in vitro inhibit α-amylase activity in dose-dependent manner. Fenugreek was more potent inhibitor than Balanites. This inhibition was reversed by increasing substrate concentration in a pattern which complies well with the effect of competitive inhibitors. Furthermore, this in vitro inhibition was confirmed by in vivo suppression of starch digestion and absorption induced by both plant extracts in normal rats. These findings suggest that the hypoglycemic effect of Fenugreek and Balanites is mediated through insulinomimetic effect as well as inhibition of intestinal α-amylase activity.     

Effects of dietary chromium and zinc on egg production, egg quality, and some blood metabolites of laying hens reared under low ambient temperature

This experiment was conducted to evaluate the effects of chromium (chromium picolinate, CrPic) and zinc (ZnSO₄·H₂O) on egg production, egg quality, and serum insulin, corticosterone, glucose, cholesterol, and total protein concentrations of laying hens reared under a low ambient temperature (6.8°C). One hundred twenty laying hens (Hy-Line; 32 wk old) were divided into 4 groups, 30 hens per group. The laying hens were fed the control diet (T1) or the control diet supplemented with either 400 μg of Cr/kg of diet (T2), 30 mg of Zn/kg of diet (T3), or 400 μg of Cr plus 30 mg of Zn/kg of diet (T4). Although the dry matter intake (DMI) was similar (p>0.05) for all treatment groups, supplemental chromium and zinc either individually or together increased live-weight change, egg production, and improved feed efficiency (p<0.05). However, no significant differences were observed between T4 and T2 or T3. Compared to T1, supplemental chromium and zinc increased egg weight, eggshell weight, eggshell thickness, egg specific gravity, and Haugh unit (p<0.05) in T2, T3, and T4 groups, among which there was no significant difference. Serum insulin concentration increased (p<0.05) and corticosterone concentration decreased (p<0.05) with dietary chromium and zinc supplementation. Serum glucose and cholesterol concentrations decreased (p<0.05) and protein concentrations increased (p<0.001) with dietary chromium and zinc supplementation in all treatment groups. The results of this study indicated that either supplemental dietary chromium or zinc increased plasma insulin and decreased corticosterone concentrations and that had a positive effect on performance of laying hens under low ambient temperature.     

Hypoglycemic activity and mechanism of the sulfated rhamnose polysaccharides chromium(III) complex in type 2 diabetic mice

The sulfated rhamnose polysaccharides found in Enteromorpha prolifera belong to a class of unique polyanionic polysaccharides with high chelation capacity. In this study, a complex of sulfated rhamnose polysaccharides with chromium(III) (SRPC) was synthesized, and its effect on type 2 diabetes mellitus (T2DM) in mice fed a high-fat, high-sucrose diet was investigated. The molecular weight of SRPC is 4.57 kDa, and its chromium content is 28 μg/mg. Results indicated that mice treated by oral administration of SRPC (10 mg/kg and 30 mg/kg body mass per day) for 11 weeks showed significantly improved oral glucose tolerance, decreased body mass gain, reduced serum insulin levels, and increased tissue glycogen content relative to T2DM mice (p < 0.01). SRPC treatment improved glucose metabolism via activation of the IR/IRS-2/PI3K/PKB/GSK-3β signaling pathway (which is related to glycogen synthesis) and enhanced glucose transport through insulin signaling cascade–induced GLUT4 translocation. Because of its effectiveness and stability, SRPC could be used as a therapeutic agent for blood glucose control and a promising nutraceutical for T2DM treatment.     

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.     

The Preventive Effect of Nicotinic Acid on Carbon Tetrachloride Toxicity in Sheep

The blood glucose response following the intravenous injection of butyric acid, 2.5 mM/kg, was studied in normal and carbon tetrachloride poisoned sheep. In normal sheep there was a rapid increase in blood glucose. Carbon tetrachloride greatly reduced the glucose response. In animals pretreated with nicotinic acid, 50 mg/kg, on the day before carbon tetrachloride administration, the glucose response was not altered. When a larger dose of nicotinic acid, 100 mg/kg, was given simultaneously with carbon tetrachloride, the glucose response was reduced more than after only carbon tetrachloride. Nicotinic acid alone at the dose of 100 mg/kg reduced the glucose rise somewhat more than carbon tetrachloride. There was a good agreement between the glucose rise following butyric acid and the glycogen content of the liver. It thus seemed clear that butyric acid has a glycogenolytic effect when given intravenously. Carbon tetrachloride caused severe necrosis and fatty changes in the liver. These pathological changes were reduced by pretreating the animals with 50 mg/kg of nicotinic acid. The larger dose of nicotinic acid, 100 mg/kg, caused a diffuse degeneration of the liver cells and a complete disappearence of glycogen. All liver injuries were followed by a rise in serum OCT.     

Effects of Se-enriched polysaccharides produced by Enterobacter cloacae Z0206 on alloxan-induced diabetic mice

In this study, the water-soluble selenium-enriched exopolysaccharides (Se-ECZ-EPS) were isolated from submerged culture broth of Enterobacter cloacae Z0206 through fermentation, ethanol precipitation and deproteinization. The protective effects of Se-ECZ-EPS on alloxan-induced diabetic mice were investigated. Diabetes was induced in ICR (Institute of Cancer Research) mice by administration of single doses of alloxan intraperitoneally (190 mg/kg body weight). Se-ECZ-EPS at a dose of 200 mg/kg body weight were administered per os (p.o.) as single dose per day to diabetes-induced mice for a period of 42 days. The decrease in body weight, serum insulin level, and the increase in blood glucose level, glycosylated serum protein (GSP), total cholesterol (TC) and triglycerides (TG) in liver were observed in diabetic mice. On the other hand, oral administration of Se-ECZ-EPS resulted in a significant reduction in fasting blood glucose levels, GSP, TC and TG contents in liver coupled with improvement of body weight and serum insulin level in comparison with diabetic control group. These results suggest that Se-ECZ-EPS possess significant protective and anti-diabetic effects in alloxan-induced diabetic mice.