Pancreatic adaptation in VMH obesity: in vivo compensatory response to altered neural input.
The objective of these studies was to determine the impact of enhanced insulin response to glucose (glucose responsiveness) and altered neurotransmitter sensitivity of the pancreatic islet previously observed after ventromedial hypothalamic (VMH) lesion on the glucose regulatory system in the whole animal. Female Wistar (220 g) rats received bilateral electrolytic VMH lesions and were implanted with cardiac and femoral cannulas under anesthesia. After recovery, experimental studies were conducted in 2-h-fasted lightly heparinized conscious rats. Plasma glucose declined at 1 and 2 wk after lesion and returned gradually to basal levels by 4 wk, whereas plasma insulin was elevated at 1 wk and remained elevated at 4.5 wk after lesion. Glucose responsiveness was increased threefold 1 wk after lesion. Acetylcholine sensitivity, measured by insulin response to an acetylcholine analogue, was decreased at 1, 2, and 4 wk after lesion, whereas norepinephrine sensitivity, measured by norepinephrine inhibition of the insulin response to intravenous glucose, was significantly increased 1 wk after VMH lesion. These studies suggest that the observed alterations at the level of the pancreatic islet led to a shift in the operating point of the glucose regulatory system of the whole animal and that changes in neurotransmitter sensitivity reflect a pancreatic adaptation subsequent to the establishment of enhanced glucose responsiveness. This shift in operating point may be secondary to altered neural input and may be essential to pancreatic and, thus, metabolic adaptation to the VMH lesion-induced obese state.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D007033:Hypothalamus, Middle / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D000109:Acetylcholine; D009638:Norepinephrine