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 journalArticlepeer-review

32 Scopus citations


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
Issue number1
StatePublished - Jul 1994
Externally publishedYes


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

ASJC Scopus subject areas

  • Medicine(all)


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