TY - JOUR

T1 - Impaired expression of glycogen synthase mRNA in skeletal muscle of NIDDM patients

AU - Vestergaard, H

AU - Bjørbaek, C

AU - Andersen, P H

AU - Bak, J F

AU - Pedersen, O

PY - 1991/12

Y1 - 1991/12

N2 - Based on recent studies of the abnormal physiology and biochemistry of the glycogen synthesis in skeletal muscle of non-insulin-dependent diabetes mellitus (NIDDM) patients and their first-degree relatives, the key enzyme of this pathway, glycogen synthase (GS), is considered a candidate gene in the pathogenesis of insulin resistance. Comparing matched groups of 14 NIDDM patients with 14 control subjects, we found that impaired insulin-stimulated nonoxidative glucose metabolism of peripheral tissue (P less than 0.02) and reduced total GS activity (P less than 0.05) of vastus lateralis muscle from patients with NIDDM were accompanied by a 39% reduction (P less than 0.02) in the steady state level of GS mRNA per microgram DNA of muscle. In both diabetic and control subjects, the mRNA expression of GS was unaffected after euglycemic-hyperinsulinemic clamp for 4 h. With single-stranded conformation polymorphism analysis of the entire coding sequence of the GS gene, we were unable to detect any genetic variants in a subset of eight NIDDM patients. We conclude that abnormal pretranslational regulation of the GS gene may contribute to impaired glycogen synthesis of muscle in NIDDM. Our studies give no evidence for structural changes in the coding region of the GS gene, and it is unknown if the decreased mRNA expression is due to impaired transcription or accelerated degradation of the transcript.

AB - Based on recent studies of the abnormal physiology and biochemistry of the glycogen synthesis in skeletal muscle of non-insulin-dependent diabetes mellitus (NIDDM) patients and their first-degree relatives, the key enzyme of this pathway, glycogen synthase (GS), is considered a candidate gene in the pathogenesis of insulin resistance. Comparing matched groups of 14 NIDDM patients with 14 control subjects, we found that impaired insulin-stimulated nonoxidative glucose metabolism of peripheral tissue (P less than 0.02) and reduced total GS activity (P less than 0.05) of vastus lateralis muscle from patients with NIDDM were accompanied by a 39% reduction (P less than 0.02) in the steady state level of GS mRNA per microgram DNA of muscle. In both diabetic and control subjects, the mRNA expression of GS was unaffected after euglycemic-hyperinsulinemic clamp for 4 h. With single-stranded conformation polymorphism analysis of the entire coding sequence of the GS gene, we were unable to detect any genetic variants in a subset of eight NIDDM patients. We conclude that abnormal pretranslational regulation of the GS gene may contribute to impaired glycogen synthesis of muscle in NIDDM. Our studies give no evidence for structural changes in the coding region of the GS gene, and it is unknown if the decreased mRNA expression is due to impaired transcription or accelerated degradation of the transcript.

KW - Blotting, Northern

KW - DNA

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Gene Expression Regulation, Enzymologic

KW - Glucose Clamp Technique

KW - Glycogen Synthase

KW - Humans

KW - Insulin

KW - Insulin Infusion Systems

KW - Male

KW - Middle Aged

KW - Muscles

KW - Polymorphism, Genetic

KW - RNA, Messenger

KW - Reference Values

M3 - Journal article

C2 - 1756915

VL - 40

SP - 1740

EP - 1745

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -