Hypoglycemic and hypolipidemic effects of aqueous extract of Arachis hypogaea in normal and alloxan-induced diabetic rats.

The hypoglycemic and hypolipidemic effect of aqueous extract of Arachis hypogaea was investigated in normal and alloxan-induced diabetic rats. The extract caused a significant (P < 0.05) decrease of fasting blood glucose of both normal and alloxan-induced diabetic rats from 102.60 +/- 1.65 mg/dl to 88.79 +/- 0.94 mg/dl for normal and 189.0 +/- 30.79 mg/dl to 107.55 +/- 1.54 mg/dl for alloxan-induced diabetic rats. The extract also caused a significant (P < 0.05) decrease in serum triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol in both normal and alloxan-induced diabetic rats.     

Role of insulin in regulation of high density lipoprotein metabolism

The effect of alloxan-induced insulin deficiency on high density lipoprotein (HDL) metabolism was studied in rabbits. Rabbits with alloxan-induced diabetes had significantly higher (P less than 0.001, mean +/- SEM) plasma concentrations of glucose (541 +/- 13 vs. 130 +/- 2 mg/dl), triglyceride (2851 +/- 332 vs. 101 +/- 10 mg/dl), and total plasma cholesterol (228 +/- 55 vs. 42 +/- 4 mg/dl) than did normal control rabbits. However, diabetic rabbits had lower plasma HDL-cholesterol (7.2 +/- 1 vs. 51.3 +/- 1.3 mg/dl, P less than 0.001) and HDL apoA-I (38.3 +/- 6.0 vs. 87.2 +/- 4.3 mg/dl, P less than 0.001) concentrations. HDL kinetics were compared in diabetic and normal rabbits, using either 125I-labeled HDL or HDL labeled with 125I-labeled apoA-I, and it was demonstrated that HDL fractional catabolic rate (FCR) was slower and residence time was longer in the diabetic rabbits when either tracer was used. The slow FCR and the low apoA-I pool size led to reduced apoA-I/HDL synthetic rate in diabetic rabbits (0.97 +/- 0.11 vs. 0.34 +/- 0.07 mg per kg per hr). Thus, the reduced plasma HDL-cholesterol concentrations seen in rabbits with alloxan-induced insulin deficiency was associated with a lower total apoA-I/HDL synthetic rate. Since insulin treatment restored to normal all of the changes in plasma lipoprotein concentration and kinetics seen in diabetic rabbits, it is unlikely that the phenomena observed were secondary to a nonspecific toxic effect of alloxan. These data strongly support the view that insulin plays an important role in regulation of HDL metabolism.     

Developing a new model for non-insulin dependent diabetes mellitus (NIDDM) by using the Philippine wild mouse, Mus musculus castaneus.

The Philippine wild-caught castaneus mouse (Mus musculus castaneus) and laboratory mouse (C57BL/6J: B6) were used to develop a new non-insulin dependent diabetes mellitus (NIDDM) model. Offspring from the cross between a wild male and B6 female were backcrossed to the sire. One male which exhibited highest fasting hyperglycemia (190 mg/dl) among eighty-seven backcross offspring was selected at 10 weeks of age, and crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed to develop a new inbred strain named CBD (Castaneus-B6 diabetic) mouse. Mice with relatively higher fasting hyperglycemia among F0 and F1 generations were selected for breeding. From the F2 generation, mice were defined as diabetic when blood glucose levels exceeded 200 mg/dl at 120 min in intraperitoneal glucose tolerance test (IPGTT) at 10 weeks of age, and have been selectively bred. The incidence of diabetic males from the F3-F6 generation fluctuated 45-75% at 10 weeks of age and 59-72% at 20 weeks of age. Diabetic males had about two-fold higher fasting glucose and insulin levels than B6 males. Glucose-stimulated insulin secretion was impaired in diabetic CBD mice compared to B6 males at 20 weeks. Moreover, diabetic mice had slight obesity compared to B6 mice. These facts indicated that diabetic features of CBD mice resemble NIDDM in humans. The CBD strain, characterized by high incidence and early onset of diabetes with mild obesity would be of value as a new NIDDM model. The method, utilizing wild castaneus mouse of different origin from laboratory mice, maybe useful in the development of other animal models.     

Shift in metabolic substrate uptake by the heart during development of alloxan-induced diabetes

Inhibition of endothelial nitric oxide (NO) synthase (eNOS) is associated with an increase in glucose uptake by the heart. We have already shown that Type I diabetes also causes a decrease in eNOS protein expression and altered NO control of both coronary vascular resistance and oxygen consumption. Therefore, we predict that the increase in plasma glucose and the reduction in eNOS during diabetes together would result in a large increase in cardiac glucose uptake. Arterial (A) and coronary sinus (C) plasma levels of glucose, free fatty acid (FFA), beta-hydroxybutyric acid (beta-HBA), and lactate were measured, and myocardial uptake was calculated before and at week 1, 2, 3, and 4 of alloxan-induced diabetes. The heart of healthy dogs consumed FFA (19.2 +/- 2.6 microeq/min) and lactate (19.7 +/- 3.4 micromol/min). Dogs in the late stage of diabetes (at week 4) had elevated arterial beta-HBA concentrations (1.6 +/- 0.7 micromol/l) that were accompanied by an increased beta-HBA uptake (0.3 +/- 0.2 micromol/min). In contrast, myocardial lactate (-4.8 +/- 3.0 micromol/min) and FFA uptake (2.5 +/- 1.9 microeq/min) were significantly reduced in diabetic animals. Despite a marked hyperglycemia (449 +/- 25 mg/dl), the heart did not take up glucose (-7.9 +/- 4.1 mg/dl). Our results indicate significant changes in the myocardial substrate utilization in dogs only in the late stage of diabetes, at a time when myocardial NO production is already decreased.     

The antidiabetic activity of aloes: preliminary clinical and experimental observations

The dried sap of the aloe plant (aloes) is one of several traditional remedies used for diabetes in the Arabian peninsula. Its ability to lower the blood glucose was studied in 5 patients with non-insulin-dependent diabetes and in Swiss albino mice made diabetic using alloxan. During the ingestion of aloes, half a teaspoonful daily for 4-14 weeks, the fasting serum glucose level fell in every patient from a mean of 273 +/- 25 (SE) to 151 +/- 23 mg/dl (p less than 0.05) with no change in body weight. In normal mice, both glibenclamide (10 mg/kg twice daily) and aloes (500 mg/kg twice daily) induced hypoglycaemia after 5 days, 71 +/- 6.2 and 91 +/- 7.6 mg/dl, respectively, versus 130 +/- 7 mg/dl in control animals (p less than 0.01); only glibenclamide was effective after 3 days. In the diabetic mice, fasting plasma glucose was significantly reduced by glibenclamide and aloes after 3 days. Thereafter only aloes was effective and by day 7 the plasma glucose was 394 +/- 22.0 versus 646 +/- 35.9 mg/dl, in the controls and 726 +/- 30.9 mg/dl in the glibenclamide treated group (p less than 0.01). We conclude that aloes contains a hypoglycaemic agent which lowers the blood glucose by as yet unknown mechanisms.     

Hyperglycemia-induced insulin resistance in diabetic dyslipidemic Yucatan swine

Hyperglycemia, dyslipidemia, and associated insulin resistance are hallmarks of diabetes mellitus. Purposes of the study reported here were to develop practical methods for assessment of in vivo insulin sensitivity and determine contributions of hyperglycemia and dyslipidemia to insulin resistance in the porcine model of alloxan-induced diabetes mellitus and dyslipidemia. Male Yucatan swine groups were treated for 20 weeks: control (C), high fat-fed (2% cholesterol) hyperlipidemic (H), alloxan-induced diabetic normolipidemic (D), diabetic high fat-fed (diabetic dyslipidemic, DD), and diabetic dyslipidemic treated with the lipid-lowering agent atorvastatin (DDA). Plasma cholesterol concentration increased sixfold in animals of groups H, DD, and DDA, whereas triglyceride concentration increased threefold in animals of group DD only. Diabetics had decreases in glucose tolerance and pancreatic immunostaining for insulin. Use of the gold standard hyperinsulinemic euglycemic clamp procedure indicated that maximal insulin-stimulated glucose uptake was similar to that in humans, but this method was not practical for use in pigs. Instead, a more convenient and valid insulin sensitivity test involving suppression of insulin secretion with somatostatin and a single insulin injection was used. Insulin sensitivity was greatly impaired by anesthesia with isoflurane, but was not affected by use of the anxiolytic agent diazepam. Insulin sensitivity decreased by 75% in diabetics (groups D, DD, DDA), compared with animals of groups C and H, and was inversely related to fasting blood glucose concentration (r = -0.72). Insulin treatment to restore blood glucose values of diabetics (> 250 mg/dl) to near control values (< 100 mg/dl) promptly restored insulin sensitivity to control values. We conclude that hyperglycemia is a major cause of insulin resistance in the porcine model of alloxan-induced diabetes mellitus and dyslipidemia.     

Anti-diabetic effect of ginsenoside Re in ob/ob mice

We evaluated the anti-diabetic effects of ginsenoside Re in adult male C57BL/6J ob/ob mice. Diabetic ob/ob mice with fasting blood glucose levels of approximately 230 mg/dl received daily intraperitoneal injections of 7, 20 and 60 mg/kg ginsenoside Re for 12 consecutive days. Dose-related effects of ginsenoside Re on fasting blood glucose levels were observed. After the 20 mg/kg treatment, fasting blood glucose levels were reduced to 188+/-9.2 and 180+/-10.8 mg/dl on Day 5 and Day 12, respectively (both P<0.01 compared to vehicle group, 229+/-9.5 and 235+/-13.4 mg/dl, respectively). The EC(70) of ginsenoside Re was calculated to be 10.3 mg/kg and was used for subsequent studies. Consistent with the reduction in blood glucose, there were significant decreases in both fed and fasting serum insulin levels in mice treated with ginsenoside Re. With 12 days of ginsenoside treatment, glucose tolerance of ob/ob mice increased significantly, and the area under the curve for glucose decreased by 17.8% (P<0.05 compared to vehicle treatment). The hypoglycemic effect of the ginsenoside persisted even at 3 days of treatment cessation (blood glucose levels: 198+/-13.1 with ginsenoside treatment vs. 253+/-20.3 mg/dl with vehicle, P<0.01). There were no significant changes in body weight or body temperature. Preliminary microarray analysis revealed differential expression of skeletal muscle genes associated with lipid metabolism and muscle function. The results suggest that ginsenoside Re may prove to be useful in treating type 2 diabetes.     

Type 2 diabetes mellitus in a non-obese mouse model induced by Meg1/Grb10 overexpression

We assessed the possibility of C57BL/6-Tg (Meg1/Grb10)isn(Meg1 Tg) mice as a non-obese type 2 diabetes (2DM) animal model. Meg1 Tg mice were born normal, but their weight did not increase as much as normal after weaning and showed about 85% of normal size at 20 weeks of age. Body mass index of Meg1 Tg mice was also smaller than that of control mice. The glucose tolerance test and insulin tolerance test showed that Meg1 Tg mice had reduced ability to normalize the blood glucose level. Blood urea nitrogen (BUN) in Meg1 Tg mice (19.6 +/- 1.2 mg/dl) was significantly lower than in controls (22.0 +/- 0.8 mg/dl), while plasma triglyceride, insulin, adiponectin, and resistin levels were significantly higher (202.0 +/- 23.4 mg/dl vs 146.3 +/- 23.4 mg/dl, 152.4 +/- 16.3 pg/ml vs 88.1 +/- 16.9 pg/ml, 74.4 +/- 10.9 microg/ml vs 48.3 +/- 7.0 microg/ml, and 4.0 +/- 0.2 ng/ml vs 3.6 +/- 0.2 ng/ml, respectively). Body, visceral fat weight and liver weights were significantly lower (19.6 +/- 0.4 g vs 24.3 +/- 0.3 g, 376.7 +/- 29.6 mg to 507.5 +/- 23.0 mg, and 906.0 +/- 41.8 mg to 1,001.0 +/- 15.1 mg, respectively). Thus, hyperinsulinemia observed in Meg1 Tg mice indicates that their insulin signaling pathway is somehow inhibited. With high fat diet, the diabetes onset rate of Meg1 Tg mice increased up to 60%. These results suggest that Meg1 Tg mice resemble human 2DM.     

Diabetes and hyperglycemia impair activation of mitochondrial K(ATP) channels

Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (K(ATP)) channels. Acutely instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of the area at risk (AAR) for infarction in control, diabetic (3 wk after streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs, respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10 +/- 1% of AAR, P < 0.05) but did not produce protection in the presence of diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl; 23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3, 15 +/- 3 (P < 0.05), and 11 +/- 2% (P < 0.05), respectively]. There were no differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by radioactive microspheres) between groups. The results indicate that diabetes or hyperglycemia impairs activation of mitochondrial K(ATP) channels.     

Changes in insulin response to glucose after exercise training in partially pancreatectomized rats

The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T less than 200 and Unt less than 200 (glucose concn less than 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T greater than 300 and Unt greater than 300 (glucose concn greater than 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations less than 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T less than 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt less than 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T greater than 300 (0.36 +/- 0.2) vs Unt greater than 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (less than 300 mg/dl) diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucose monitoring at the thenar: evaluation of upper dermal blood glucose kinetics during rapid systemic blood glucose changes.

OBJECTIVE: We compared blood glucose measurements at the thenar with those at the fingertip during glucose increase and decrease that was rapid enough to induce glucose differences between the forearm and the fingertip. METHODS: A rapid glucose increase was induced by oral glucose; subsequently, a rapid glucose decrease was induced by intravenous insulin in 16 insulin-treated patients with diabetes. Capillary samples were taken in parallel from the thenar and fingertip. Different glucose monitors (FreeStyle, OneTouch Ultra, Soft-Sense) were used. Additional samples were taken from the forearm (n = 10 patients) in order to demonstrate that the blood glucose change achieved was rapid enough to principally induce glucose differences at alternative sites. RESULTS: Neither blood glucose at baseline (135 +/- 34 vs. 136 +/- 41 mg/dl, p = 0.86) nor glucose amplitude during increase (190 +/- 35 vs. 188 +/- 41 mg/dl, p = 0.65) or decrease (255 +/- 32 vs. 257 +/- 45 mg/dl, p = 0.83) differed significantly between the fingertip and the thenar. Intra-individual average thenar-fingertip glucose difference was - 2 +/- 12 (p = 1.00) and + 5 +/- 9 mg/dl (p = 0.11). In the subgroup, intra-individual average forearm-finger difference was - 50 +/- 19 (p < 0.01) and + 45 +/- 11 mg/dl (p < 0.01) during glucose-increase and decrease, respectively. There were no obvious device-specific differences. CONCLUSIONS: Blood glucose measurements at the thenar are a safe alternative to measurements at the fingertip at steady state as well as during blood glucose change that is sufficiently rapid to induce clinically relevant differences between forearm and fingertip.     

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.     

Cardioprotection by glucose-insulin-potassium: dependence on KATP channel opening and blood glucose concentration before ischemia

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K(+) (K(ATP)) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml x kg(-1) x h(-1)) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of K(ATP) channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 +/- 2% of the area at risk in control experiments. GIK decreased (P < 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 +/- 2 and 12 +/- 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 +/- 4%), hyperglycemia before ischemia (27 +/- 4%), or diabetes (25 +/- 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 +/- 3, 27 +/- 2, and 35 +/- 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by K(ATP) channel activation. However, glucose decreases K(ATP) channel activity, and this effect predominates when hyperglycemia is present before ischemia.     

Effect of obesity on erythrocyte count and hemoglobin levels in Libyan diabetic patients

Fasting blood glucose, erythrocyte count and hemoglobin levels of obese and nonobese Libyan diabetic women were determined. The mean values of fasting blood glucose, erythrocyte count and hemoglobin of obese diabetic women were 209.55 +/- 8.85 mg/dl, 4.986 +/- 0.04 X 10(6)/mm3 and 14.51 +/- 0.18 g/dl. The respective values for nonobese diabetic women were 243.47 +/- 12.56 mg/dl, 4.865 +/- 0.06 X 10(6)/mm3 and 14.31 +/- 0.19 g/dl. The mean values of the three variables of obese patients were significantly different from those of the nonobese patients. Statistically significant correlations were found between fasting blood glucose levels and erythrocyte count, and hemoglobin levels in both obese and nonobese patients. The levels of erythrocyte count and hemoglobin of obese patients were higher than those of their nonobese counterparts. This elevation was attributed to the effect of obesity. It is suggested that regulation of body weight should be considered an essential step in the management of diabetes.     

Effect of a high protein diet on glucose tolerance in the rat model

The purpose of this study was to determine the effects of a high protein diet on glucose tolerance. Nine Sprague Dawley rats received a high protein (HP) diet (65% protein, 35% fat) and eight rats consumed a standard chow (SC) diet over eight weeks. Oral glucose tolerance tests (OGTT) were performed at the end of the third and the seventh week. The diet did not effect glucose tolerance in the first (SC=10357+/-294 mg/dl/120 min; HP=9846+/-300 mg/dl/120 min) or the second OGTT (SC=10134+/-395 mg/dl/120 min; HP=10721+/-438 mg/dl/120 min) as reflected by the area under the glucose concentration curve. Similarly, the area under the insulin concentration curve was not effected by the high protein diet during the first (SC=49.21+/-8.46 ng/ml/120 min; HP=41.75+/-10.54 ng/ml/120 min) or the second OGTT (SC=96.63+/-13.68 ng/ml/120 min; HP=92.77+/-17.44 ng/ml/120 min). The high protein diet group experienced a delayed glucose response for the first (SC=30 min at 112+/-7 mg/dl; HP=60 min at 101+/-5 mg/dl) and second OGTT (SC=15 min at 117+/-5 mg/dl; HP=60 min at 95+/-7 mg/dl). Body mass increased to the same extent in each diet group from the initial to final weighing (SC=159+/-2 g to 254+/-7 g; HP=157+/-2 g to 242+/-7 g). Despite a delay in peak glucose response, these findings suggest that glucose tolerance and body mass were neither adversely nor positively affected by a high protein diet.     

Correlations between blood glucose levels and bromodeoxyuridine labelling indices of pancreatic islet cells following streptozotocin administration to pregnant Syrian golden hamsters

Eighteen timed-pregnant Syrian golden hamsters were injected subcutaneously with streptozotocin (STZ, 60 mg/kg bw) early on gestational day 10. The response varied widely, and based on changes in blood glucose levels during gestational days 11 to 15, the hamsters were categorized into four groups: 1) no change; 2) mild diabetes (200-250 mg/dl), which reverted; 3) moderate diabetes (greater than 300 mg/dl), which reverted; and 4) moderate to severe diabetes (300-500 mg/dl), which was sustained. Two hours before sacrifice, a 25 mg tablet of bromodeoxyuridine (BrdU) was implanted subcutaneously into each experimental hamster and into 17 control pregnant hamsters that had not received STZ. BrdU-labelling was demonstrated immunochemically in the pancreatic islet cells. In control hamsters, the mean labelling index (LI) of the islet cells was 0.07% and did not exceed 0.2% in any hamster. Following injection of STZ, islet cell LI's remained low (0.13%) if the blood glucose levels were not altered by the diabetogenic drug. However, LI's were increased in islet cells of hamsters which showed a mild to moderate diabetes which rapidly reverted; the highest LI's (5% +/- 2.1) occurred in four hamsters that were killed 2 days after receiving STZ. The LI's were moderately increased (1.4% +/- 0.42) in two hamsters with moderate diabetes killed 2 days after STZ, but LI's were low (0.12% +/- 0.04) in six hamsters with moderate to severe diabetes killed 3, 4, and 5 days after STZ. Reversion of hyperglycemia to normoglycemia correlated closely with increased DNA synthesis in the islet cells of the pregnant hamsters. These observations strongly suggest that following mild cytotoxic injury induced by STZ, the B cells regenerated and insulin production was restored sufficiently to maintain normoglycemia.     

Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice

Hypoglycemia-induced counterregulatory failure is a dangerous complication of insulin use in diabetes mellitus. Controlled hypoglycemia studies in gene knockout models, which require the use of mice, would aid in identifying causes of defective counterregulation. Because stress can influence counterregulatory hormones and glucose homeostasis, we developed glucose clamps with remote blood sampling in conscious, unrestrained mice. Male C57BL/6 mice implanted with indwelling carotid artery and jugular vein catheters were subjected to 2 h of hyperinsulinemic glucose clamps 24 h apart, with a 6-h fast before each clamp. On day 1, blood glucose was maintained (euglycemia, 178 +/- 4 mg/dl) or decreased to 62 +/- 1 mg/dl (hypoglycemia) by insulin (20 mU x kg(-1) x min(-1)) and variable glucose infusion. Donor blood was continuously infused to replace blood sample volume. Baseline plasma epinephrine (32 +/- 8 pg/ml), corticosterone (16.1 +/- 1.8 microg/dl), and glucagon (35 +/- 3 pg/ml) were unchanged during euglycemia but increased significantly during hypoglycemia, with a glycemic threshold of approximately 80 mg/dl. On day 2, all mice underwent a hypoglycemic clamp (blood glucose, 64 +/- 1 mg/dl). Compared with mice that were euglycemic on day 1, previously hypoglycemic mice had significantly higher glucose requirements and significantly lower plasma glucagon and corticosterone (n = 6/group) on day 2. Epinephrine tended to decrease, although not significantly, in repeatedly hypoglycemic mice. Pre- and post-clamp insulin levels were similar between groups. We conclude that counterregulatory responses to acute and repeated hypoglycemia in unrestrained, chronically cannulated mice reproduce aspects of counterregulation in humans, and that repeated hypoglycemia in mice is a useful model of counterregulatory failure.     

Increased dependence on blood glucose after acclimatization to 4,300 m

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-hyperglycemic effects of ginseng: Comparison between root and berry

Previous studies demonstrated that both ginseng root and ginseng berry possess anti-diabetic activity. However, a direct comparison between the root and the berry under the same experimental conditions has not been conducted. In the present study, we compared anti-hyperglycemic effect between Panax ginseng root and Panax ginseng berry in ob/ob mice, which exhibit profound obesity and hyperglycemia that phenotypically resemble human type-2 diabetes. We observed that ob/ob mice had high baseline glucose levels (195 mg/dl). Ginseng root extract (150 mg/kg body wt.) and ginseng berry extract (150 mg/kg body wt.) significantly decreased fasting blood glucose to 143 +/- 9.3 mg/dl and 150 +/- 9.5 mg/dl on day 5, respectively (both P < 0.01 compared with the vehicle). On day 12, although fasting blood glucose level did not continue to decrease in the root group (155 +/- 12.7 mg/dl), the berry group became normoglycemic (129 +/- 7.3 mg/dl; P < 0.01). We further evaluated glucose tolerance using the intraperitoneal glucose tolerance test. On day 0, basal hyperglycemia was exacerbated by intraperitoneal glucose load, and failed to return to baseline after 120 min. After 12 days of treatment with ginseng root extract (150 mg/kg body wt.), the area under the curve (AUC) showed some decrease (9.6%). However, after 12 days of treatment with ginseng berry extract (150 mg/kg body wt.), overall glucose exposure improved significantly, and the AUC decreased 31.0% (P < 0.01). In addition, we observed that body weight did not change significantly after ginseng root extract (150 mg/kg body wt.) treatment, but the same concentration of ginseng berry extract significantly decreased body weight (P < 0.01). These data suggest that, compared to ginseng root, ginseng berry exhibits more potent anti-hyperglycemic activity, and only ginseng berry shows marked anti-obesity effects in ob/ob mice.     

Non-invasive glucose monitoring in patients with diabetes: a novel system based on impedance spectroscopy

The aim of this work was to evaluate the performance of a novel non-invasive continuous glucose-monitoring system based on impedance spectroscopy (IS) in patients with diabetes. Ten patients with type 1 diabetes (mean+/-S.D., age 28+/-8 years, BMI 24.2+/-3.2 kg/m(2) and HbA(1C) 7.3+/-1.6%) and five with type 2 diabetes (age 61+/-8 years, BMI 27.5+/-3.2 kg/m(2) and HbA(1C) 8.3+/-1.8%) took part in this study, which comprised a glucose clamp experiment followed by a 7-day outpatient evaluation. The measurements obtained by the NI-CGMD and the reference blood glucose-measuring techniques were evaluated using retrospective data evaluation procedures. Under less controlled outpatient conditions a correlation coefficient of r=0.640 and a standard error of prediction (SEP) of 45 mg dl(-1) with a total of 590 paired glucose measurements was found (versus r=0.926 and a SEP of 26 mg dl(-1) under controlled conditions). Clark error grid analyses (EGA) showed 56% of all values in zone A, 37% in B and 7% in C-E. In conclusion, these results indicate that IS in the used technical setting allows retrospective, continuous and truly non-invasive glucose monitoring under defined conditions for patients with diabetes. Technical advances and developments are needed to expand on this concept to bring the results from the outpatient study closer to those in the experimental section of the study. Further studies will not only help to evaluate the performance and limitations of using such a technique for non non-invasive glucose monitoring but also help to verify technical extensions towards a IS-based concept that offers improved performance under real life operating conditions.