Effects of a 7-day infusion of glucose on insulin secretion in vivo and in vitro in ventromedial hypothalamic-lesioned obese rats.
Excessive stimulation of insulin secretion may be one cause of the beta-cell dysfunction induced by hyperglycemia. We investigated a possible link between the prior endogenous hypersecretion of insulin and this dysfunction by performing a 7-day glucose infusion (50% wt/vol, 1.2 ml/h) on ventromedial hypothalamic VMH-lesioned hyperinsulinemic rats. Intravenous glucose tolerance tests (i.v.GTT 1.0 g/kg) revealed that a 3-day glucose infusion enhanced the insulin responses in both the sham- and VMH-lesioned rats compared with saline infusions. A similar 7-day glucose infusion enhanced the insulin response to glucose in sham-lesioned rats but not in VMH-lesioned rats. Batch-incubation of islets isolated from sham-lesioned rats showed an enhanced insulin response to glucose after 7 days of glucose treatment compared with the saline infusions. Conversely, the glucose infusion in VMH-lesioned rats markedly suppressed the in vitro insulin response. In sham- and VMH-lesioned rats, similar islet insulin contents were produced by saline and glucose treatments. Electron microscopy revealed that glucose infusions impaired the granule-releasing function of the beta-cells in VMH-lesioned rats, while insulin synthesis was accelerated in either group. These findings support the notion that excessive secretion is partly responsible for the beta-cell dysfunction induced by hyperglycemia without signs of exhaustion.
Kuboi
M
M
The Third Department of Internal Medicine, Yokohama City University, Yokohama, Japan.
Egawa
M
M
Udaka
N
N
Ito
T
T
Inoue
S
S
Sekihara
H
H
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007033:Hypothalamus, Middle / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose