Effects of oral carbohydrate on autonomic nervous system counterregulatory responses during hyperinsulinemic hypoglycemia and euglycemia

Abstract

The effects of oral carbohydrate on modulating counterregulatory responses in humans remain undecided. This study's specific aim was to determine the effects of oral carbohydrate on autonomic nervous system (ANS) and neuroendocrine responses during hyperinsulinemic hypoglycemia and euglycemia. Nineteen healthy volunteers were studied during paired, single blind experiments. Nine subjects underwent two-step glucose clamps consisting of 60 min of euglycemia (5.0 mmol/l) followed by either 15 g of oral carbohydrate (cal) as orange juice or a noncaloric control (nocal) and subsequent 90 min of clamped hypoglycemia (2.9 mmol/l). Ten other subjects underwent two randomized 150-min hyperinsulinemic-euglycemic clamps with cal or nocal control administered at 60 min. Oral carbohydrate initially blunted (P < 0.05) epinephrine, norepinephrine, cortisol, glucagon, pancreatic polypeptide, muscle sympathetic nerve activity (MSNA), symptom, and systolic blood pressure responses during hypoglycemia. However, by the end of 90 min of hypoglycemia, plasma epinephrine and norepinephrine responses had rebounded and were increased (P < 0.05) compared with control. MSNA and cortisol levels remained suppressed during hypoglycemia (P < 0.05) after cal, whereas pancreatic polypeptide, glucagon, symptom, and blood pressure responses increased similar to control following initial suppression. Oral carbohydrate had no effects on neuroendocrine or ANS responses during hyperinsulinemic euglycemia. These results demonstrate that oral carbohydrate can have differential effects on the time course of ANS and neuroendocrine responses during hypoglycemia. We conclude that gastro-splanchnic-portal sensing of an amount of carbohydrate recommended for use in clinical practice for correction of hypoglycemia can have widespread and significant effects on central nervous system mediated counterregulatory responses in healthy humans.

Ketogenesis evaluation in perfused liver of diabetic rats submitted to short‐term insulin‐induced hypoglycemia

“…administration of insulin or insulin plus glucose. Thus, it seems that the increased release of counter regulatory hormones during IIH 19,20 overcomes the inhibitory effect of insulin and/or glucose on liver ketogenesis also in diabetic rats, as previously demonstrated to non-diabetic rats. 6 To verify this possibility we investigated the ketogenesis in situ perfused livers of 24-h fasted diabetic rats submitted to short-term IIH.…”

Portal Vein Glucose Sensors Do Not Play a Major Role in Modulating Physiological Responses to Insulin-Induced Hypoglycemia in Humans

“…The above two independent calculations yield similar conclusions, i.e., the oral glucose administration in the present study successfully met the goal of prevention of portal hypoglycemia during systemic hypoglycemia. Our results are at variance with previous studies in humans (5)(6)(7). However, only one study aimed at prevention of portal hypoglycemia after administration of 20 g oral glucose (6).…”

“…Only three studies (5-7) have addressed the question, with conflicting results. In fact, counterregulatory hormone responses to hypoglycemia have been found potentiated (5), reduced (6), or reduced in early phase and potentiated in late phase (7) after ingestion of oral glucose (5,6) or orange juice (7). It is likely that methodological differences account, at least in part, for these divergent results.…”

Hypoglycemic Detection at the Portal Vein

“…The authors conclude that the portal glucose sensor plays no significant role in hypoglycemic detection for humans. This is not the first time such an approach has been employed in an attempt to elucidate the potential role of portal glucose sensing in humans (12)(13)(14). While all previous reports demonstrated a significant impact of an oral glucose load on the hormonal responses to hypoglycemia, results have been anything but consistent.…”