Glutamate pathways mediate somatostatin responses to glucose in normal and diabetic rat hypothalamus.
We investigated the role of hypothalamic glutamate receptors in mediating the stimulatory effect of low glucose (< 5 mM) on somatostatin release. We also studied whether alteration in glutamate release might contribute to the reduced hypothalamic somatostatin response to low glucose observed in diabetic (Goto-Kakizaki) rat hypothalami. Hypothalamic somatostatin release in response to incubation with 1 mM D-glucose was inhibited by the ionotropic glutamate receptor antagonists MK801, D-AP5 and DNQX but not by the metabotropic antagonists L-AP3 or MCPG. The release of somatostatin was increased by the ionotropic agonists NMDA, AMPA and kainate but not by metabotropic agonists t-ACPD or L-AP4. Basal and peak glutamate release in response to incubation with 1 mM glucose, were significantly lower from GK hypothalami There were no significant differences in the basal or stimulated release of serine and GABA. These data indicate that ionotropic NMDA/AMPA/kainate receptors and not metabotropic receptors mediate the effects of glucose on rat hypothalamic somatostatin release. Reduced hypothalamic somatostatin release in response to low glucose in diabetic (Goto-Kakizaki) rats may well be secondary, at least in part, to reduced glutamate release.
Issa
B G
BG
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Lewis
B M
BM
Ham
J
J
Peters
J R
JR
Scanlon
M F
MF
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012016:Reference Values; D013004:Somatostatin / Q000378:metabolism*
D000596:Amino Acids; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D013004:Somatostatin; D005947:Glucose