Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

Abstract

A B S T R A C T The existence of a relationship between the ventromedial hypothalamic area (VMH) and the activity of the endocrine pancreas has been shown previously. This relationship has been further tested and extended in the present study, using isolated perfused pancreases from rats previously lesioned (4-7 d) in the VMH. It was found that in isolated pancreases obtained from rats fed ad lib. for 4 d after VMH lesions (i.e., that were hyperphagic), the typical biphasic pattern of insulin secretion was observed following glucose stimulation (20 mM) and that the total insulin output was much greater than that of controls. The increased insulin output was not a result of hyperphagia because similar results were obtained using pancreases obtained from VMH-lesioned rats in which a food restriction matching exactly that ofcontrol rats was started either immediately or 3 d after the lesions. Pancreases from such food-restricted VMHlesioned rats oversecreted insulin, when compared with controls fed the same amount, from 7 mM of glucose concentration in perfusion medium onwards. After the addition of arginine (10 mM), the total output of glucagon by pancreases from food-restricted VMHlesioned rats was twice that of controls. Qualitatively, the arginine-induced glucagon secretion by pancreases from food-restricted VMH-lesioned rats retained its biphasic pattern. Similarly, epinephrine (0.1 ,uM) elicited a greater glucagon release by pancreases from food-restricted VMH-lesioned rats when compared with controls. These data further support the concept of a link (as yet undefined) between the hypothalamus and the endocrine pancreas, as lesions of the VMH area resulted in abnormal secretion not only of insulin, but of glucagon as well.

Genetic influences on glucose neurotoxicity, aging, and diabetes: A possible role for glucose hysteresis

“…Similar results were obtained in two other strains of mice (CBA/N and C57B1/6J). GTG-induced elevations of plasma insulin are consistent with other studies reporting that pancreatic hypersecretion of both insulin and glucagon occurs within minutes of an electrolytic VMH lesion in rats (Berthoud & Jeanrenaud, 1979;Rohner-Jeanrenaud & Jeanrenaud, 1980;Rotmer-Jeanrenaud & Jenrenaud, t 984), well before hyperphagia or insulin resistance develops (Jeanrenaud, Halimi & Van de Werve, 1985). In addition, VMH lesions cause hypersecretion of pancreatic islet polypeptide (amylin) (Tokuyama et al, 1991).…”

Functional identification of a neurocircuit regulating blood glucose

“…From a teleological perspective, it makes intuitive sense that, when glucose availability is threatened, responses that increase glucose production would be activated (e.g., elevated glucagon and corticosterone levels) in concert with responses that reduce glucose clearance (e.g., inhibition of insulin secretion), and much of the literature indicates that pancreatic beta cells are subject to inhibitory control via the sympathetic nervous system (SNS) (47,48). For example, bilateral VMN lesioning induces hyperinsulinemia (49,50) whereas electrical stimulation of the VMN suppresses glucose-induced insulin secretion (51). Further, the VMN is known to regulate autonomic outflow to the pancreas (52,53), and activation of islet sympathetic nerves during glycopenic stress (54) inhibits insulin secretion via a mechanism involving activation of α2-adrenoreceptors on the beta cell (47,48).…”

Pediatric Endocrine Disorders of Energy Balance

“…Intracellular calcium influx increases acutely, which results in rapid insulin vesicular exocytosis. Concomitant opening of the sodium channel by vagally-mediated acetylcholine augments β-cell depolarization, which in turn augments the intracellular calcium influx, and results in insulin hypersecretion [83,90,91]. 2.…”