1998 Fiscal Year Final Research Report Summary
Significance of glycogen synthase gene mutation in NIDDM
| Project/Area Number |
09671068
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Wakayama Medical Collage |
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Principal Investigator |
NANJO Kishio Wakayama Medical Collage, Professor, 医学部・内科学第一講座, 教授 (40164511)
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| Co-Investigator(Kenkyū-buntansha) |
HANABUSA Tadashi Wakayama Medical Collage, Assistant Professor, 医学部・内科学第一講座, 助手 (40198784)
SANKE Tokio Wakayama Medical Collage, Associate Professor, 医学部・内科学第一講座, 助教授 (20187305)
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| Project Period (FY) |
1997 – 1998
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| Keywords | NIDDM / glycogen synthase |
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| Research Abstract |
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 : x 10(-4) x min(-1) x (microU/ml)(-1)] estimated by Minimal Model analysis in the NlDDM 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.
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