Differential sensitivity of growth hormone-releasing hormone and somatostatin release from perifused mouse hypothalamic fragments in response to glucose deficiency.
The effects of glucose deficiency on growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) release from mouse hypothalamic fragments were investigated using an in vitro perifusion system. Fragments were perifused with Krebs-Ringer bicarbonate solution (KRB) containing 5.6 mM glucose for 3 h followed by reduced glucose concentrations in KRB for the next 2 h. GRH release was simulated by 0.7-2.8 mM glucose in an inverse concentration-dependent manner. In contrast, SRIH release was not stimulated by glucose at concentrations of 2.8 and 1.4 mM; only at 0.7 mM was there a modest stimulation of SRIH release that was comparable to the effect of 2.8 mM glucose on GRH release. The maximal stimulation of GRH and SRIH release by 0.7 mM glucose was 221 and 150%, respectively, of controls. Glucose concentrations of 11.2 and 22.4 mM inhibited GRH release but did not alter SRIH release. The glucose analog 2-deoxy-D-glucose (2-DG; 5.6-39.2 mM) also stimulated GRH release in a dose-dependent manner, and SRIH release was less sensitive to 2-DG than was GRH. The maximal stimulation of GRH and SRIH release by 39.2 mM 2-DG was 190 and 147%, respectively, of controls. Increases in GRH and SRIH release stimulated by 30 mM KCl 1 h after exposure to low glucose or 2-DG were not significantly different from those after exposure to 5.6 mM glucose. However, the SRIH response to K(+)-induced depolarization was much greater than that of GRH. The glucose intermediate pyruvate (4.9 and 9.8 mM) partially inhibited both GRH and SRIH release induced by 0.7 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Sato
M
M
Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio.
Frohman
L A
LA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency* / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D051379:Mice; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D011863:Radioimmunoassay; D013004:Somatostatin / Q000378:metabolism*
D000596:Amino Acids; D000927:Anticonvulsants; D007202:Indicators and Reagents; D011773:Pyruvates; D013004:Somatostatin; D011189:Potassium Chloride; D015763:2-Amino-5-phosphonovalerate; D019289:Pyruvic Acid; D013007:Growth Hormone-Releasing Hormone; D003847:Deoxyglucose; D005947:Glucose; C031231:2-amino-7-phosphonoheptanoic acid