Glycogen synthase: A putative locus for diet-induced hyperglycemia

Michael F Seldin, David Mott, Deepti Bhat, Ann Petro, Cynthia M. Kuhn, Stephen F. Kingsmore, Clifton Bogardus, Emmanuel Opara, Mark N. Feinglos, Richard S. Surwit

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Inbred mouse strains fed a diabetogenic diet have different propensities to develop features analogous to type 2 diabetes mellitus. To define chromosomal locations that control these characteristics, recombinant inbred strains from diabetes-prone C57BL/6J (B/6J) and diabetes-resistant A/J strains were studied. Insulin levels and hyperglycemia correlated with two different regions of mouse chromosome 7 (two point LOD scores > 3.0). For insulin levels, 15 of 16 recombinant inbred strains were concordant with a region that contains the tubby mutation that results in hyperinsulinemia. For hyperglycemia, 19 of 23 strains were concordant with the D7Mit25 marker and 20 of 23 strains with the Gpi-1 locus on proximal mouse chromosome 7. Using more stringent criteria for hyperglycemia, 10 of 11 strains characterized as A/J or B/6J like were concordant with D7Mit25. This putative susceptibility locus is consistent with that of the glycogen synthase gene (Gys) recently suggested as a candidate locus by analyses of type 2 diabetes patients. Fractional glycogen synthase activity in isolated muscle was significantly lower in normal B/6J diabetic-prone mice compared with normal diabetic- resistant A/J mice, a finding similar to that reported in relatives of human patients with type 2 diabetes. These data, taken together, raise the possibility that defects in the Gys gene may in part be responsible for the propensity to develop type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)269-276
Number of pages8
JournalJournal of Clinical Investigation
Volume94
Issue number1
StatePublished - Jul 1994
Externally publishedYes

Fingerprint

Glycogen Synthase
Hyperglycemia
Type 2 Diabetes Mellitus
Diet
Chromosomes, Human, Pair 7
Insulin
Genes
Inbred Strains Mice
Hyperinsulinism
Muscles
Mutation

Keywords

  • diet
  • genetics
  • glycogen synthase
  • mouse
  • non-insulin dependent diabetes mellitus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Seldin, M. F., Mott, D., Bhat, D., Petro, A., Kuhn, C. M., Kingsmore, S. F., ... Surwit, R. S. (1994). Glycogen synthase: A putative locus for diet-induced hyperglycemia. Journal of Clinical Investigation, 94(1), 269-276.

Glycogen synthase : A putative locus for diet-induced hyperglycemia. / Seldin, Michael F; Mott, David; Bhat, Deepti; Petro, Ann; Kuhn, Cynthia M.; Kingsmore, Stephen F.; Bogardus, Clifton; Opara, Emmanuel; Feinglos, Mark N.; Surwit, Richard S.

In: Journal of Clinical Investigation, Vol. 94, No. 1, 07.1994, p. 269-276.

Research output: Contribution to journalArticle

Seldin, MF, Mott, D, Bhat, D, Petro, A, Kuhn, CM, Kingsmore, SF, Bogardus, C, Opara, E, Feinglos, MN & Surwit, RS 1994, 'Glycogen synthase: A putative locus for diet-induced hyperglycemia', Journal of Clinical Investigation, vol. 94, no. 1, pp. 269-276.
Seldin MF, Mott D, Bhat D, Petro A, Kuhn CM, Kingsmore SF et al. Glycogen synthase: A putative locus for diet-induced hyperglycemia. Journal of Clinical Investigation. 1994 Jul;94(1):269-276.
Seldin, Michael F ; Mott, David ; Bhat, Deepti ; Petro, Ann ; Kuhn, Cynthia M. ; Kingsmore, Stephen F. ; Bogardus, Clifton ; Opara, Emmanuel ; Feinglos, Mark N. ; Surwit, Richard S. / Glycogen synthase : A putative locus for diet-induced hyperglycemia. In: Journal of Clinical Investigation. 1994 ; Vol. 94, No. 1. pp. 269-276.
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