Increased glucose phosphorylating activity correlates with insulin secretory capacity of male JCR:LA-corpulent rat islets.
In this study the glucose responsiveness of isolated, overnight-cultured islets of obese LA/N-corpulent (cp/cp) rats was compared with glucose phosphorylating activity to determine whether changes in the function of glucokinase could be identified. Islets from both male and female cp/cp rats showed a left-shifted concentration response to glucose, with EC50 values of 1.5 and 4.6 mM, respectively, compared with 9.2 mM for lean control islets. Islets from cp/cp rats were partially resistant to inhibition by mannoheptulose, a glucokinase inhibitor. Minimum inhibitory concentrations were 10 mM in cp/cp vs. 3 mM in lean rat islets. Glucose phosphorylating potential was markedly increased in islets of male cp/cp, but not female cp/cp, compared with lean rats. The maximal velocity (Vmax) of hexokinase was increased 5-fold, while the Km of glucokinase was significantly decreased, in male cp/cp compared with the lean control islets(3.6 vs. 35.2 mM). The Km for glucokinase was also decreased in female cp/cp rat islets (17.2 mM). The data from male cp/cp rat islets are consistent with the idea that increased glucose phosphorylation capacity can contribute to insulin hypersecretion and an extreme leftward shift in the concentration-response curve. However, other factors must also be considered because female cp/cp rats have moderately increased insulin secretory capacity without marked changes in total glucose phosphorylating capacity.
Chan
C B
CB
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
MacPhail
R M
RM
Kibenge
M T
MT
Russell
J C
JC
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D008356:Mannoheptulose; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose