Abnormal glucose metabolism in hypertensive mice with genetically interrupted gamma-melanocyte stimulating hormone signaling fed a high-sodium diet.
BACKGROUND
Rodents with deficiency of or resistance to the proopiomelanocortin-derived peptide gamma-melanocyte stimulating hormone (gamma-MSH) develop marked salt-sensitive hypertension. We asked whether this hypertension was accompanied by abnormal glucose metabolism.


METHODS
gamma-MSH-deficient Pc2(-/-) mice, and resistant Mc3r(-/-) mice were studied acutely for measurement of blood pressure and glucose and insulin concentrations after > or =1 week of a high-sodium diet (HSD; 8% NaCl) compared to a normal-sodium diet (NSD; 0.4% NaCl). Mc3r(-/-) also underwent glucose tolerance test (GTT) and insulin tolerance test.


RESULTS
Both knockout strains were hypertensive and also exhibited fasting hyperglycemia and hyperinsulinemia on the HSD. Mc3r(-/-) mice on the HSD had impaired glucose tolerance and insulin-mediated glucose disposal compared to wild-type mice on either the HSD or the NSD, or to Mc3r(-/-) mice on the NSD.


CONCLUSIONS
These results indicate an interaction of interrupted gamma-MSH signaling with the HSD to cause hypertension on the one hand and abnormal glucose metabolism, with the characteristics of insulin resistance, on the other. Further study of the nature of this interaction should provide new insight into the mechanisms by which salt-sensitive hypertension and insulin resistance are linked.
Ni
X-P
XP
Division of Nephrology, San Francisco General Hospital, San Francisco, CA, USA.
Humphreys
Michael H
MH
D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012965:Sodium Chloride / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D019825:gamma-MSH / Q000172:deficiency* / Q000235:genetics
D007328:Insulin; D017673:Sodium Chloride, Dietary; D019825:gamma-MSH; D012965:Sodium Chloride; D005947:Glucose