A missense mutation of the muscle glycogen synthase gene (M416V) is associated with insulin resistance in the Japanese population |
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Authors: | H Shimomura T Sanke K Ueda T Hanabusa S Sakagashira K Nanjo |
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Institution: | (1) First Department of Medicine, Wakayama University of Medical Science, Wakayama, Japan, JP |
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Abstract: | Summary Muscle glycogen synthase (GYS1) is a key enzyme of non-oxidative pathway of glucose metabolism that has been reported to
be related to insulin resistance in non-insulin-dependent diabetic (NIDDM) patients. We scanned the GYS1 gene for mutation
by single strand conformational polymorphism in 244 non-obese Japanese NIDDM patients and 181 non-diabetic control subjects,
and found two missense mutations; Met to Val at position 416 in the exon 10 (M416V) and Pro to Ala at position 442 in the
exon 11 (P442A). The P442A mutation was found in only one NIDDM patient treated with sulfonylureas. On the other hand, the
M416V mutation was widely found in the Japanese population. The mutant allele frequency in the NIDDM patients (13.7 %) was
slightly higher but not statistically significant compared with that in non-diabetic subjects (9.7 %). However, the insulin
sensitivity index SI: × 10− 4× min− 1× (μU/ml)− 1] estimated by Minimal Model analysis in the NIDDM patients carrying the M416V mutation was significantly lower than that
in those without the mutation (1.18 ± 0.27, n = 21 vs 2.20 ± 0.20, n = 60, mean ± SEM, p < 0.01). Glucose effectiveness, age, body mass index, and levels of glycated haemoglobin and serum lipids were not significantly
different between the two groups. The same trend could be seen in non-diabetic subjects (SI: 3.70 ± 0.46, 9 subjects with
the mutation vs 5.94 ± 0.66, 19 subjects without the mutation, p < 0.05). These findings indicate that the M416V mutation of the GYS1 gene is one of the factors contributing to the insulin
resistance in the Japanese population and may play some role in the pathogenesis of NIDDM. Diabetologia (1997) 40: 947–952]
Received: 7 February 1997 and in revised form: 10 April 1997 |
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Keywords: | Muscle glycogen synthase insulin resistance NIDDM genetics |
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