Glycogen synthase: a putative locus for diet-induced hyperglycemia.
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.
Seldin
M F
MF
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Mott
D
D
Bhat
D
D
Petro
A
A
Kuhn
C M
CM
Kingsmore
S F
SF
Bogardus
C
C
Opara
E
E
Feinglos
M N
MN
Surwit
R S
RS
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006006:Glycogen Synthase / Q000032:analysis / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
D001786:Blood Glucose; D007328:Insulin; D006006:Glycogen Synthase