Effect of exercise training and chronic glyburide treatment on glucose homeostasis in diabetic rats

1992 ◽  
Vol 72 (1) ◽  
pp. 143-148 ◽  
Author(s):  
L. J. Goodyear ◽  
M. F. Hirshman ◽  
E. D. Horton ◽  
E. S. Horton

Exercise training and sulfonylurea treatment, either individually or in combination, were evaluated for their effects on plasma glucose concentrations, oral glucose tolerance, and glucose clearance in the perfused hindquarter of diabetic rats. Female rats that were injected with streptozocin (45 mg/kg iv) and had plasma glucose concentrations between 11 and 25 mM were considered diabetic and divided into sedentary, glyburide-treated, exercise-trained, and glyburide-treated plus exercise-trained groups. The sedentary streptozocin-treated rats were severely diabetic, as indicated by elevated glucose concentrations, impaired insulin response during oral glucose tolerance tests, and lower rates of glucose clearance in hindlimb skeletal muscle. Neither 8 wk of exercise training nor 4 wk of glyburide treatment alone improved these parameters. In contrast, the diabetic rats that were both trained and treated with glyburide showed some improvement in glucose homeostasis, as evidenced by lower plasma glucose concentrations, an enhanced insulin response to an oral glucose load, and a decrease in the severity of skeletal muscle insulin resistance compared with the diabetic controls. These data suggest that glyburide treatment or exercise training alone does not alter glucose homeostasis in severely insulin-deficient diabetic rats; however, the combination of exercise training and glyburide treatment may interact to improve glucose homeostasis in these animals.

1988 ◽  
Vol 65 (2) ◽  
pp. 844-851 ◽  
Author(s):  
L. J. Goodyear ◽  
M. F. Hirshman ◽  
S. M. Knutson ◽  
E. D. Horton ◽  
E. S. Horton

The effect of 8-wk of treadmill training on plasma glucose, insulin, and lipid concentrations, oral glucose tolerance, and glucose uptake in the perfused hindquarter of normal and streptozocin-treated, diabetic Sprague-Dawley rats was studied. Diabetic rats with initial plasma glucose concentrations of 200-450 mg/dl and control rats were divided into trained and sedentary subgroups. Training resulted in lower plasma free fatty acid concentrations and increased triceps muscle citrate synthase activity in both the control and diabetic rats; triglyceride concentrations were lowered by training only in the diabetic animals. Oral glucose tolerance and both basal and insulin-stimulated glucose uptake in hindquarter skeletal muscle were impaired in the diabetic rats, and plasma glucose concentrations (measured weekly) gradually increased during the experiment. Training did not improve the hyperglycemia, impaired glucose tolerance, or decreased skeletal muscle glucose uptake in the diabetic rats, nor did it alter these parameters in the normal control animals. In considering our results and those of previous studies in diabetic rats, we propose that exercise training may improve glucose homeostasis in animals with milder degrees of diabetes but fails to cause improvement in the more severely insulin-deficient, diabetic rat.


1986 ◽  
Vol 112 (2) ◽  
pp. 263-266 ◽  
Author(s):  
Inge Buch ◽  
Peter J. Hornnes ◽  
Claus Kühl

Abstract. The effect of pregnancy on oral glucose tolerance (50 g of glucose) and plasma insulin and glucagon responses to oral glucose was studied in weeks 10 and 32 of pregnancy and again 1 year post partum in 12 normal women. Already in week 10, fasting plasma glucose was decreased and the glucose-induced insulin secretion increased as compared with post partum. However, glucose tolerance was not affected at this time. In week 32, glucose tolerance had deteriorated, although the levels of both fasting and glucose-induced insulin were higher than those found in early pregnancy and post partum. At all investigations fasting plasma glucagon and the suppression of plasma glucagon after oral glucose were similar, indicating that glucagon is not implicated in the changes in glucose homeostasis seen in pregnancy. It is concluded that glucose tolerance is unaltered by pregnancy in week 10. Pregnancy has, however, at this very early stage already affected glucose homeostasis as seen by the decrease in fasting plasma glucose and the increase in the insulin response to glucose.


2021 ◽  
Vol 13 (1) ◽  
pp. e2021051
Author(s):  
Vincenzo De Sanctis ◽  
Ashraf Soliman ◽  
Ploutarchos Tzoulis ◽  
Shahina Daar ◽  
Salvatore Di Maio ◽  
...  

  Background: Glucose dysregulation (GD), including prediabetes and diabetes mellitus (DM), is a common complication of transfusion dependent β-thalassemia (TDT) patients. The prevalence increases with age and magnitude of iron overload, affecting a significant proportion of patients. The development of GD is frequently asymptomatic and therefore an early diagnosis, according to the international guidelines, requires an annual oral glucose tolerance test (OGTT) in all TDT patients aged ten years or older.   Purpose: This retrospective study aims to evaluate the prevalence of GD in a homogenous population of prepubertal TDT patients and to enhance understanding of the pathogenesis and progression of glucose homeostasis in this group of patients.   Methods: A selected group of 28 TDT patients was followed for at least 10.3 years (range: 10.3 - 28.10 years) from prepubertal age (mean 11.0 ± standard deviation 1.1 years) to adulthood (28.7 ± 3.7 years). Glucose tolerance and insulin response to OGTT were assessed, and indices of β-cell function, insulin sensitivity and insulin secretion were calculated.   Results: At baseline, 18 TDT patients had normal glucose tolerance (NGT) and 10 isolated impaired fasting glycaemia (IFG), according to the American Diabetes Association (ADA) criteria. Compared to 18 prepubertal healthy controls (mean ± SD age: 10.9 ± 1.1 years), the fasting plasma glucose (FPG), basal insulin level and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were significantly higher in the group of TDT patients (p= 0.001, 0.01 and 0.012, respectively). At the last observation, 7/18 patients (38.8%) with NGT and 9/10 (90%) with IFG at baseline deteriorated; 3 female patients developed type 2 DM (1 from the NGT group and 2 from the IFG group). Compared to adult controls, TDT patients with NGT had a reduced oral disposition index (DI) (p= 0.006), but no significant difference in HOMA-IR and Matsuda index. Conversely, all insulin indices (HOMA-IR, MI and DI) but one [insulinogenic index (IGI)] were statistically different in TDT patients with GD compared to controls.   Conclusion: This study shows a spectrum of disturbances in glucose homeostasis among TDT patients and that prepubertal patients with IFG are at higher risk for developing a deterioration of glucose metabolism.  


1996 ◽  
Vol 81 (1) ◽  
pp. 318-325 ◽  
Author(s):  
D. R. Dengel ◽  
R. E. Pratley ◽  
J. M. Hagberg ◽  
E. M. Rogus ◽  
A. P. Goldberg

The decline in glucose homeostasis with aging may be due to the physical deconditioning and obesity that often develop with aging. The independent and combined effects of aerobic exercise training (AEX) and weight loss (WL) on glucose metabolism were studied in 47 nondiabetic sedentary older men. There were 14 men in a weekly behavioral modification/WL program, 10 in a 3 times/wk AEX program, 14 in an AEX+WL program, and 9 in the control (Con) group. The 10-mo intervention increased maximal oxygen consumption (VO2max) in both the AEX and AEX+WL groups [0.33 +/- 0.05 and 0.37 +/- 0.09 (SE) l/min, respectively], but VO2max did not significantly change in the WL (0.01 +/- 0.06 l/min) and Con groups (-0.04 +/- 0.05 l/min; P > 0.05). The AEX+WL and WL groups had comparable reductions in body weight (-8.5 +/- 0.9 and -8.8 +/- 1.2 kg, respectively) and percent fat (-5.5 +/- 0.7 and -5.9 +/- 1.1%, respectively) that were significantly greater than those in the Con and AEX groups. Oral glucose tolerance tests showed significant reductions in insulin responses in the AEX, WL, and AEX+WL groups, but the decrease in insulin response in the AEX+WL group was significantly greater than that in the other three groups. The glucose area decreased significantly in the WL and AEX+WL groups but did not change in the Con or AEX groups. There were significant increases in insulin-mediated glucose disposal rates as measured by the hyperinsulinemic (600 pmol.m-2.min-1) euglycemic clamps in the AEX and AEX+WL groups [1.66 +/- 0.50 and 1.76 +/- 0.41 mg.kg fat-free mass (FFM)-1.min-1, respectively] that were significantly greater than those in the WL (0.13 +/- 0.31 mg.kg FFM-1.min-1) and Con groups (-0.05 +/- 0.51 mg.kg FFM-1.min-1; n = 5). These data suggest that AEX and WL improve glucose metabolism through different mechanisms and that the combined intervention of AEX+WL is necessary to improve both glucose tolerance and insulin sensitivity in older men.


1993 ◽  
Vol 264 (6) ◽  
pp. E855-E862 ◽  
Author(s):  
V. A. Hughes ◽  
M. A. Fiatarone ◽  
R. A. Fielding ◽  
B. B. Kahn ◽  
C. M. Ferrara ◽  
...  

A decline in insulin sensitivity is associated with aging, inactivity, and obesity. The effects of exercise training on glucose homeostasis independent of weight loss in older glucose-intolerant individuals are not well established. We examined the effects of exercise training on oral glucose tolerance, insulin action, and concentration of the GLUT-4 glucose transporters in skeletal muscle. Exercise training at 50 and 75% of heart rate reserve was performed for 12 wk in 18 individuals (age = 64 +/- 2, body fat = 37.0 +/- 1.5%). Peripheral insulin action was determined 96 h after the last exercise bout using a two-step hyperinsulinemic-euglycemic glucose clamp (insulin = 192 and 708 pmol/l). Percent body fat and fat-free mass (FFM) were unchanged with training. Diet composition, assessed by diet record, did not change over the 12 wk. Improved oral glucose tolerance was observed, as exhibited by lower plasma glucose concentrations after training (P < 0.05), whereas plasma insulin response remained unchanged. The rate of glucose disposal was unchanged during the low insulin concentration but increased 11.0% at the high insulin concentration (P < 0.05) after training (54.4 +/- 4.4 vs. 60.4 +/- 5.5 mumol.kg FFM-1.min-1). Skeletal muscle glycogen and GLUT-4 concentration increased 24 and 60%, respectively, with training. There was no direct relationship between the change in GLUT-4 protein and the change in glucose disposal rate. These findings demonstrate that chronic exercise training without changes in body composition improves peripheral insulin action in subjects with impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)


2003 ◽  
Vol 88 (10) ◽  
pp. 4559-4564 ◽  
Author(s):  
Soffia Gudbjörnsdóttir ◽  
Mikaela Sjöstrand ◽  
Lena Strindberg ◽  
John Wahren ◽  
Peter Lönnroth

Abstract To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle. Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp. PS for glucose increased significantly from 0.29 ± 0.1 to 0.64 ± 0.2 ml/min·100 g after oral glucose tolerance test, and glucose uptake increased from 1.2 ± 0.4 to 2.6 ± 0.6 μmol/min·100 g (P &lt; 0.05). During one-step hyperinsulinemic clamp (plasma insulin, 1.962 pmol/liter), PS for glucose increased from 0.2 ± 0.1 to 2.3 ± 0.9 ml/min·100 g (P &lt; 0.05), and glucose uptake increased from 0.6 ± 0.2 to 5.0 ± 1.4 μmol/min·100 g (P &lt; 0.05). During the two-step clamp (plasma insulin, 1380 ± 408 and 3846 ± 348 pmol/liter), the arterial-interstitial difference and PS for insulin were constant. The PS for glucose tended to increase (P = not significant), whereas skeletal muscle blood flow increased from 4.4 ± 0.7 to 6.2 ± 0.8 ml/min·100 ml (P &lt; 0.05). The present data show that PS for glucose is markedly increased by oral glucose, whereas a further vasodilation exerted by high insulin concentrations may not be physiologically relevant for capillary delivery of either glucose or insulin in resting muscle.


2018 ◽  
Vol 5 (7) ◽  
pp. 2440-2454
Author(s):  
D. A. Omoboyowa ◽  
F. O. Afolabi ◽  
T. C. Aribigbola

Background: The anti-hyperglycemic potential of methanol stem bark extract of Anacardium occidentale (MSBEAO) was investigated using an alloxan-induced diabetic rat model. Alloxan administration induces the generation of free radicals which can affect antioxidant status resulting in the disruption of the β-cells of the pancreas. Therefore, this study examines the antioxidant potential of the plant extract and the ameliorating effect on the pancreas of alloxan-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal injection of 150 mg/kg body weight of alloxan monohydrate. MSBEAO, at a concentration of 100 or 200 mg/kg b.w. was orally administered to alloxan-induced diabetic rats and normal rats. The hypoglycemic effect, oral glucose tolerance test, and biochemical assay of alloxan-induced diabetic rats were assayed using standard procedures. Results: Preliminary phytochemical screening of the extract revealed the presence of alkaloids, tannins, saponins, terpenoids, carbohydrates, and phenols at moderate concentrations. The lethality dose (LD50) of the plant extract was found to be equal to or less than 5000 mg/kg b.w. The hypoglycemic effect of the extract on the non-diabetic rats revealed a significant (p<0.05) decrease in the blood glucose concentration of animals administered with 1 g/kg b.w. of the extract, compared to normal control rats administered with normal saline. In the oral glucose tolerance test, the methanol extract exerted the highest response, similar to glibenclamide after 15 and 30 minutes of administration, compared to the control rats. The methanol extract yielded the highest blood glucose lowering effects after 9 days of treatment (p<0.05), compared to diabetic rats administered with normal saline and 0.3 mg/kg b.w. of glibenclamide. Administration of the extract at 200 mg/kg b.w. showed improved pancreas architecture and regeneration of the β-cells, compared with the pancreas of animals in the other groups. Conclusion: The results of this study suggest that MSBEAO is a potentially effective agent for the management of diabetes which might result from the antioxidant-generating capacity of the stem bark.


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