Prior exercise and the response to insulin-induced hypoglycemia in the dog

Abstract

Prior exercise and the response to insulin-induced hypoglycemia in the dog. Am J Physiol Endocrinol Metab 282: E1128-E1138, 2002; 10.1152/ ajpendo.00370.2001.-To test whether hepatic insulin action and the response to an insulin-induced decrement in blood glucose are enhanced in the immediate postexercise state as they are during exercise, dogs had sampling (artery, portal vein, and hepatic vein) catheters and flow probes (portal vein and hepatic artery) implanted 16 days before a study. After 150 min of moderate treadmill exercise or rest, dogs were studied during a 150-min hyperinsulinemic (1 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) euglycemic (n ϭ 5 exercised and n ϭ 9 sedentary) or hypoglycemic (65 mg/dl; n ϭ 8 exercised and n ϭ 9 sedentary) clamp. Net hepatic glucose output (NHGO) and endogenous glucose appearance (Ra) and utilization (Rd) were assessed with arteriovenous and isotopic ([3-3 H]glucose) methods. Results show that, immediately after prolonged, moderate exercise, in relation to sedentary controls: 1) the glucose infusion rate required to maintain euglycemia, but not hypoglycemia, was higher; 2) Rd was greater under euglycemic, but not hypoglycemic conditions; 3) NHGO, but not Ra, was suppressed more by a hyperinsulinemic euglycemic clamp, suggesting that hepatic glucose uptake was increased; 4) a decrement in glucose completely reversed the enhanced suppression of NHGO by insulin that followed exercise; and 5) arterial glucagon and cortisol were transiently higher in the presence of a decrement in glucose. In summary, an increase in insulin action that was readily evident under euglycemic conditions after exercise was abolished by moderate hypoglycemia. The means by which the glucoregulatory system is able to overcome the increase in insulin action during moderate hypoglycemia is related not to an increase in Ra but to a reduction in insulin-stimulated Rd. The primary site of this reduction is the liver. liver; metabolism; oxidation; glucose; lactate; nonesterified fatty acids IT IS WELL RECOGNIZED THAT the ability of insulin to stimulate glucose uptake is enhanced by a single bout of exercise (21). We have shown that the marked increase in insulin action during exercise is matched by an equally profound increase in insulin-induced hypoglycemic counterregulation in an exercising dog model (28). The effectiveness of this potent counterregulatory response may be important in decreasing the magnitude and frequency of hypoglycemia during a bout of exercise. Skeletal muscle remains more sensitive to insulin for a sustained period after exercise (21). In contrast, the counterregulatory response to insulininduced hypoglycemia is actually reduced a full day after prolonged exercise (9, 16). This is significant, because this likely contributes to the high risk of hypoglycemia in people with insulin-dependent diabetes (27). Whether hypoglycemic counterregulation during the interval immediately after exercise remains sensitized, as it is during exercise, or blunted, as it is after extended recovery from exercise, is unknow...

Acute, same-day effects of antecedent exercise on counterregulatory responses to subsequent hypoglycemia in type 1 diabetes mellitus

“…In contrast, in the current study, fat metabolism and nonoxidative glucose disposal were all increased after prior exercise, whereas in the 2-day study fat metabolism was reduced and glucose R d and oxidative glucose disposal were significantly greater during day 2 hypoglycemia compared with the control group. Thus our current and previous data, together with the contrasting data summarized here (27,31) suggest that duration, volume, intensity, and time elapsed after prior exercise may all influence metabolic counterregulatory responses to subsequent hypoglycemia.…”

“…Of note, there were significantly greater reductions in both NEFA and glycerol during afternoon hypoglycemia following AM HYPO or AM EX, indicating a greater utilization over production of these substrates. Thus the enhanced fat metabolism appeared to cause a degree of insulin resistance after AM HYPO, whereas, after AM EX, glucose R d was similar to control studies due to the actions of exercise to enhance glucose R d (27), thereby offsetting the effects of fat to reduce insulin sensitivity. Ninety minutes of prolonged moderate exercise were used in the present study.…”

“…Changes in these parameters (i.e., differences in duration and work intensities) appear to influence responses to subsequent hypoglycemia in nondiabetic individuals, as other studies examining same dayeffects of prior exercise on subsequent counterregulatory responses to hypoglycemia have shown divergent results. For example, prolonged exercise in dogs reduced counterregulatory responses to immediate subsequent glucoprivation (28) but not in response to subsequent hyperinsulinemic hypoglycemia (27). In nondiabetic humans, one bout of prolonged exercise (60 min at 60% V O 2 max ) had no effect on counterregulatory responses to subsequent (90 min postexercise) hypoglycemia (31).…”

Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites

“…For example, it is well known that, after exercise, the sensitivity of liver glucose uptake to insulin is increased, possibly due to glycogen depletion (27). Thus, in the current study, GC (index of flux through glucokinase) may have become the rate-limiting site for insulin-induced suppression of EGP.…”

Effects of Low and Moderate Antecedent Exercise on Counterregulatory Responses to Subsequent Hypoglycemia in Type 1 Diabetes

“…For example, in dogs, prolonged exercise reduced counterregulatory responses to immediate subsequent glucoprivation (36), while in another study counterregulatory responses to subsequent hyperinsulinemic hypoglycemia appeared unaffected (37). In humans, one bout of prolonged exercise (60 min at 60% VO 2max ) in nondiabetic subjects had no effect on counterregulatory responses to subsequent (90 min postexercise) hypoglycemia (14).…”