Abstract | OBJECTIVE:
Insulin released by the beta-cell is thought to act locally to regulate glucagon secretion. The possibility that insulin might also act centrally to modulate islet glucagon secretion has received little attention. RESEARCH DESIGN AND METHODS: Initially the counterregulatory response to identical hypoglycemia was compared during intravenous insulin and phloridzin infusion in awake chronically catheterized nondiabetic rats. To explore whether the disparate glucagon responses seen were in part due to changes in ventromedial hypothalamus (VMH) exposure to insulin, bilateral guide cannulas were inserted to the level of the VMH and 8 days later rats received a VMH microinjection of either 1) anti- insulin affibody, 2) control affibody, 3) artificial extracellular fluid, 4) insulin (50 microU), 5) insulin receptor antagonist (S961), or 6) anti- insulin affibody plus a gamma-aminobutyric acid A ( GABA(A)) receptor agonist muscimol, prior to a hypoglycemic clamp or under baseline conditions. RESULTS: CONCLUSIONS: Together, these data suggest that insulin's inhibitory effect on alpha-cell glucagon release is in part mediated at the level of the VMH under both normoglycemic and hypoglycemic conditions.
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Authors | Sachin A Paranjape, Owen Chan, Wanling Zhu, Adam M Horblitt, Ewan C McNay, James A Cresswell, Jonathan S Bogan, Rory J McCrimmon, Robert S Sherwin |
Journal | Diabetes
(Diabetes)
Vol. 59
Issue 6
Pg. 1521-7
(Jun 2010)
ISSN: 1939-327X [Electronic] United States |
PMID | 20299468
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Insulin
- Glucagon
- Phlorhizin
- Proto-Oncogene Proteins c-akt
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Topics |
- 3T3 Cells
- Animals
- Glucagon
(blood, metabolism)
- Hypoglycemia
(chemically induced, prevention & control)
- Insulin
(pharmacology, physiology)
- Insulin-Secreting Cells
(metabolism)
- Male
- Mice
- Pancreas
(metabolism)
- Phlorhizin
(pharmacology)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Ventromedial Hypothalamic Nucleus
(drug effects, physiology)
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