Prevention of Overt Hypoglycemia During Exercise

Abstract

These studies were conducted to determine the magnitude and mechanism of compensation for impaired glucagon and insulin responses to exercise. For this purpose, dogs underwent surgery >16 days before experiments, at which time flow probes were implanted and silastic catheters were inserted. During experiments, glucagon and insulin were fixed at basal levels during rest and exercise using a pancreatic clamp with glucose clamped (PC/GC; n ‫؍‬ 5), a pancreatic clamp with glucose unclamped (PC; n ‫؍‬ 7), or a pancreatic clamp with glucose unclamped ؉ intraportal propranolol and phentolamine hepatic ␣-and ␤-adrenergic receptor blockade (PC/HAB; n ‫؍‬ 6). Glucose production (R a ) was measured isotopically. Plasma glucose was constant in PC/GC, but fell from basal to exercise in PC and PC/HAB. R a was unchanged with exercise in PC/GC, but was slightly increased during exercise in PC and PC/ HAB. Despite minimal increases in epinephrine in PC/ GC, epinephrine increased approximately sixfold in PC and PC/HAB during exercise. In summary, during moderate exercise, 1) the increase in R a is absent in PC/GC; 2) only a moderate fall in arterial glucose occurs in PC, due to a compensatory increase in R a ; and 3) the increase in R a is preserved in PC/HAB. In conclusion, stimulation of R a by a mechanism independent of pancreatic hormones and hepatic adrenergic stimulation is a primary defense against overt hypoglycemia. Diabetes

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m

“…In the present study, more than sixfold higher epinephrine and norepinephrine concentrations were observed during exercise at Altitude without a change in glucose R a . The role of adrenergic stimulation on hepatic glucose output during exercise is unclear; however, the data of the present study support the notion that hepatic adrenergic stimulation does not play a major role in glucose homeostasis during exercise (9,10,18).…”

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

“…Of course, this does not exclude the possibility that catecholamines are involved in the activation of hepatic MAPK signalling during exercise. Moreover, it is interesting to note that, independent of pancreatic hormones and catecholamine action, evidence exists that the fall in plasma glucose concentrations has stimulatory effects on the liver leading to enhanced glucose output [42,43]. The results from these studies suggest that a signal related to the fall in plasma glucose, e.g.…”

Exercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach

“…Interestingly, the equally rapid increase in EGP in T1D subjects during exercise despite higher glucose levels and lower glucagon concentrations, all of which would normally suppress EGP, implies that robust exercise induced hepatic responsivity despite adverse hormonal and substrate milieu, which necessitates further investigations. Factors that could contribute to this adaptive process in T1D subjects could be related to increased hepatic glucagon sensitivity stimulating glycogenolysis, increased hepatic gluconeogenesis due to enhanced substrate availability (e.g., lactate, free fatty acids), or potential blood-borne feedback and afferent mechanisms that have been shown more recently to modulate glucose R a (6,18,19).…”

“…Simultaneously, rates of endogenous glucose production (EGP) increase to minimize risks of hypoglycemia (5, 9, 31, 33). These changes in glucose fluxes are facilitated by falling insulin and rising glucagon and catecholamine (34) concentrations in plasma together with emerging roles for potential blood-borne feedback and afferent reflex mechanisms in stimulating glucose rate of appearance (R a ) (6,18,19) and pancreatic islet hormone secretion (24).However, the increment in EGP may not sufficiently compensate for the increase in glucose disposal, thus predisposing to exercise-induced hypoglycemia in type 1 diabetes (T1D) (27). This could, at least in part, be due to impaired glucagon and/or catecholamine secretion and responsiveness because of concomitant dysfunction of ␣-cell or autonomic systems, respectively, that often afflicts patients with T1D (8, 17).…”

“…Simultaneously, rates of endogenous glucose production (EGP) increase to minimize risks of hypoglycemia (5, 9, 31, 33). These changes in glucose fluxes are facilitated by falling insulin and rising glucagon and catecholamine (34) concentrations in plasma together with emerging roles for potential blood-borne feedback and afferent reflex mechanisms in stimulating glucose rate of appearance (R a ) (6,18,19) and pancreatic islet hormone secretion (24).…”