Opposite effects of acute hypoglycemia and acute hyperglycemia on glucose transport and glucose transporters in perfused rat skeletal muscle.

Mathoo, Julian; Shi, Zhi Qing; Klip, Amira; Vranić, Mladen

doi:10.2337/diabetes.48.6.1281

Cited by 29 publications

(32 citation statements)

References 40 publications

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“…The increment in MCR observed with -blockade in this study, therefore, was likely due to enhanced whole-body insulin-mediated glucose uptake, presumably at muscle and adipose tissue, independent of a rise in insulin. Hyperglycemia also downregulates glucose transporters acutely and chronically in the presence or absence of residual insulin (36,37) and restoration of normoglycemia reverses that effect (37), but the present study indicates that restoration or the normal increase in MCR with stress was due predominantly to the effect of the -blockade per se rather than to normalization of hyperglycemia with basal insulin.…”

Section: Fig 3 Plasma Concentrations Of Lactate (A) Ffa (B) and Gcontrasting

confidence: 60%

Beta-blockade, but not normoglycemia or hyperinsulinemia, markedly diminishes stress-induced hyperglycemia in diabetic dogs.

Rashid

Shi²,

Niwa³

et al. 2000

Diabetes

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Stress-induced hyperglycemia can lead to significant deterioration in glycemic control in individuals with diabetes. Previously, we have shown in normal dogs that, after intracerebroventricular (ICV) administration of carbachol (a model of moderate stress), increases in both the metabolic clearance rate (MCR) of glucose and endogenous glucose production (GP) occur. Howe v e r, in hyperglycemic diabetic dogs subjected to the same stress, the MCR of glucose does not increase and glycemia therefore markedly deteriorates because of stimulation of GP. Our aims were to determine the following: 1) whether insulin-induced acute normalization of glycemia, with or without -blockade, would correct glucose clearance and prevent the hyperglycemic eff e c t of stress, and 2) whether hyperinsulinemia per se could correct these abnormalities. Stress was induced by ICV carbachol in 27 experiments in five alloxan-administered diabetic dogs subjected to the following protocols in random order: 1) basal insulin infusion (BI) to restore normoglycemia; 2) basal insulin infusion with -blockade (BI+block); 3) normoglycemic-hyperinsulinemic clamp with threefold elevation of insulin above basal (3 BI); and 4) normoglycemic-hyperinsulinemic clamp with fivefold elevation of insulin above basal ( 5 BI). The BI+block protocol fully prevented stressinduced hyperglycemia, both by increasing MCR ( MCR at peak: 0.72 ± 0.25 m l · k g -1 · min -1 vs. no change in BI, P < 0.05) and by diminishing the stressinduced increment in GP observed in BI ( GP at peak: 3.72 ± 0.09 µmol · k g -1 · min -1 for BI+block vs. 14.10 ± 0.31 µmol · k g -1 · min -1 for BI, P < 0.0001). In contrast, 3 BI and 5 BI treatments with normoglycemichyperinsulinemic clamps proportionately increased basal MCR at baseline, but paradoxically were not associated with an increase in MCR in response to stress, which induced a twofold increase in GP. Thus, in alloxan-administered diabetic dogs, stress increased GP but not MCR, despite normalization of glycemia with basal or high insulin. In contrast, -a d r e n e r g i c blockade almost completely restored the metabolic response to stress to normal and prevented marked hyperglycemia, both by limiting the rise in GP and by increasing glucose MCR. We conclude that acute normalization of glycemia with basal insulin or hyperinsulinemia does not prevent hyperglycemic effects of stress unless accompanied by -blockade, and we speculate that short-term -blockade may be a useful treatment modality under some stress conditions in patients with diabetes. Diabetes 4 9 :2 5 3-262, 2000 T he increased demand for glucose by the brain, heart, and other tissues during stress necessitates adaptive alterations in glucose metabolism. In many forms of stress, the rate of glucose production rises above the rate of glucose clearance, resulting in hyperglycemia. It is well recognized that stress induces a greater derangement in glucose regulation in patients with diabetes than in nondiabetic individuals. Consequently, in diabetes there can be an exaggerated ...

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Section: Fig 3 Plasma Concentrations Of Lactate (A) Ffa (B) and Gcontrasting

confidence: 60%

Beta-blockade, but not normoglycemia or hyperinsulinemia, markedly diminishes stress-induced hyperglycemia in diabetic dogs.

Rashid

Shi²,

Niwa³

et al. 2000

Diabetes

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“…Increased glucose transporter numbers at the plasma membrane has been suggested as the mechanism for increased glucose uptake postexercise, and in rat skeletal muscle, a 1.8-fold increase in glucose transporters found at the plasma membrane was observed after exercise (32). The relationship between glycogen and membrane permeability to glucose is apparently reciprocal, with increasing glycogen content postexercise leading to a decrease in glucose uptake (33).…”

Section: Discussionmentioning

confidence: 99%

Control of Glycogen Synthesis by Glucose, Glycogen, and Insulin in Cultured Human Muscle Cells

et al. 2001

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A key feature of type 2 diabetes is impairment in the stimulation of glycogen synthesis in skeletal muscle by insulin. Glycogen synthesis and the activity of the enzyme glycogen synthase (GS) have been studied in human myoblasts in culture under a variety of experimental conditions. Incubation in the absence of glucose for up to 6 h caused an ϳ50% decrease in glycogen content, which was associated with a small decrease in the fractional activity of GS. Subsequent reincubation with physiological concentrations of glucose led to a dramatic increase in the rate of glycogen synthesis and in the fractional activity of GS, an effect which was both time-and glucose concentration-dependent and essentially additive with the effects of insulin. This effect was seen only after glycogen depletion. Inhibitors of signaling pathways involved in the stimulation of glycogen synthesis by insulin were without significant effect on the stimulatory action of glucose. These results indicate that at least two distinct mechanisms exist to stimulate glycogen synthesis in human muscle: one acting in response to insulin and the other acting in response to glucose after glycogen depletion, such as that which results from exercise or starvation. Diabetes 50: 720 -726, 2001

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“…We have speculated that its suppression represents a protective mechanism against hyperglycemia, and that this is the reason that muscle may not have the diabetic complications seen in organs that do not have this mechanism. Most recently, we have shown in the perfused rat hindquarter that this mechanism applies to both hyper-and hypoglycemia, and that it is due to altered translocation and synthesis of glucose transporters (53). Thus, with hypoglycemic and hyperglycemic infusions, the number of glucose transporters in plasma membrane increases and decreases, respectively.…”

Section: Effects Of Epi and Ne Infusion Of During Moderate Exercisementioning

confidence: 96%

“…Thus, with hypoglycemic and hyperglycemic infusions, the number of glucose transporters in plasma membrane increases and decreases, respectively. This is proportional to changes in GU (53).…”

Section: Effects Of Epi and Ne Infusion Of During Moderate Exercisementioning

confidence: 99%

Intense Exercise Has Unique Effects on Both Insulin Release and Its Roles in Glucoregulation

2002

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In intense exercise (>80% VO 2max ), unlike at lesser intensities, glucose is the exclusive muscle fuel. It must be mobilized from muscle and liver glycogen in both the fed and fasted states. Therefore, regulation of glucose production (GP) and glucose utilization (GU) have to be different from exercise at <60% VO 2max , in which it is established that the portal glucagon-to-insulin ratio causes the less than or equal to twofold increase in GP. GU is subject to complex regulation by insulin, plasma glucose, alternate substrates, other humoral factors, and muscle factors. At lower intensities, plasma glucose is constant during postabsorptive exercise and declines during postprandial exercise (and often in persons with diabetes). During such exercise, insulin secretion is inhibited by ␤-cell ␣-adrenergic receptor activation. In contrast, in intense exercise, GP rises seven-to eightfold and GU rises three-to fourfold; therefore, glycemia increases and plasma insulin decreases minimally, if at all. Indeed, even an increase in insulin during ␣-blockade or during a pancreatic clamp does not prevent this response, nor does pre-exercise hyperinsulinemia due to a prior meal or glucose infusion. At exhaustion, GU initially decreases more than GP, which leads to greater hyperglycemia, requiring a substantial rise in insulin for 40 -60 min to restore pre-exercise levels. Absence of this response in type 1 diabetes leads to sustained hyperglycemia, and mimicking it by intravenous infusion restores the normal response. Compelling evidence supports the conclusion that the marked catecholamine responses to intense exercise are responsible for both the GP increment (that occurs even during glucose infusion and postprandially) and the restrained increase of GU. These responses are normal in persons with type 1 diabetes, who often report exercise-induced hyperglycemia, and in whom the clinical challenge is to reproduce the recovery period hyperinsulinemia. Intense exercise in type 2 diabetes requires additional study. Diabetes 51 (Suppl. 1):S271-S283, 2002

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Opposite effects of acute hypoglycemia and acute hyperglycemia on glucose transport and glucose transporters in perfused rat skeletal muscle.

Cited by 29 publications

References 40 publications

Beta-blockade, but not normoglycemia or hyperinsulinemia, markedly diminishes stress-induced hyperglycemia in diabetic dogs.

Beta-blockade, but not normoglycemia or hyperinsulinemia, markedly diminishes stress-induced hyperglycemia in diabetic dogs.

Control of Glycogen Synthesis by Glucose, Glycogen, and Insulin in Cultured Human Muscle Cells

Intense Exercise Has Unique Effects on Both Insulin Release and Its Roles in Glucoregulation

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