GLYCOGEN-SYNTHASE AND PHOSPHOFRUCTOKINASE PROTEIN AND MESSENGER-RNA LEVELS IN SKELETAL-MUSCLE FROM INSULIN-RESISTANT PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

被引:88
作者
VESTERGAARD, H
LUND, S
LARSEN, FS
BJERRUM, OJ
PEDERSEN, O
机构
[1] AARHUS UNIV,AARHUS KOMMUNE HOSP,DIV ENDOCRINOL & METAB,INTERNAL MED CLIN C,DK-8000 AARHUS,DENMARK
[2] NOVO NORDISK,BAGSVAERD,DENMARK
关键词
NIDDM; SKELETAL MUSCLE; GLYCOGEN SYNTHASE PROTEIN; PHOSPHOFRUCTOKINASE PROTEIN; MESSENGER RNA;
D O I
10.1172/JCI116466
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In patients with non-insulin-dependent diabetes mellitus (NIDDM) and matched control subjects we examined the interrelationships between in vivo nonoxidative glucose metabolism and glucose oxidation and the muscle activities, as well as the immunoreactive protein and mRNA levels of the rate-limiting enzymes in glycogen synthesis and glycolysis, glycogen synthase (GS) and phosphofructokinase (PFK), respectively. Analysis of biopsies of quadriceps muscle from 19 NIDDM patients and 19 control subjects showed in the basal state a 30% decrease (P < 0.005) in total GS activity and a 38% decrease (P < 0.00 1) in GS mRNA/mug DNA in NIDDM patients, whereas the GS protein level was normal. The enzymatic activity and protein and mRNA levels of PFK were all normal in diabetic patients. In subgroups of NIDDM patients and control subjects an insulin-glucose clamp in combination with indirect calorimetry was performed. The rate of insulin-stimulated nonoxidative glucose metabolism was decreased by 47% (P < 0.005) in NIDDM patients, whereas the glucose oxidation rate was normal. The PFK activity, protein level, and mRNA/mug DNA remained unchanged. The relative activation of GS by glucose-6-phosphate was 33% lower (P < 0.02), whereas GS mRNA/mug DNA was 37% lower (P < 0.05) in the diabetic patients after 4 h of hyperinsulinemia. Total GS immunoreactive mass remained normal. In conclusion, qualitative but not quantitative posttranslational abnormalities of the GS protein in muscle determine the reduced insulin-stimulated nonoxidative glucose metabolism in NIDDM.
引用
收藏
页码:2342 / 2350
页数:9
相关论文
共 61 条
  • [21] DETERMINATION OF TOTAL SERUM-INSULIN (IRI) IN INSULIN-TREATED DIABETIC PATIENTS
    HEDING, LG
    [J]. DIABETOLOGIA, 1972, 8 (04) : 260 - &
  • [22] HOTHERNIELSEN O, 1987, DIABETOLOGIA, V30, P834
  • [23] THE PROTEIN PHOSPHATASES INVOLVED IN CELLULAR-REGULATION .6. MEASUREMENT OF TYPE-1 AND TYPE-2 PROTEIN PHOSPHATASES IN EXTRACTS OF MAMMALIAN-TISSUES - AN ASSESSMENT OF THEIR PHYSIOLOGICAL ROLES
    INGEBRITSEN, TS
    STEWART, AA
    COHEN, P
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1983, 132 (02): : 297 - 307
  • [24] ITAYA K, 1965, J LIPID RES, V6, P16
  • [25] LILLY LECTURE 1979 - ROLE OF INSULIN IN THE REGULATION OF PROTEIN-SYNTHESIS
    JEFFERSON, LS
    [J]. DIABETES, 1980, 29 (06) : 487 - 496
  • [26] IMPAIRED ACTIVATION OF SKELETAL-MUSCLE GLYCOGEN-SYNTHASE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS IS UNRELATED TO THE DEGREE OF OBESITY
    JOHNSON, AB
    ARGYRAKI, M
    THOW, JC
    JONES, IR
    BROUGHTON, D
    MILLER, M
    TAYLOR, R
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 1991, 40 (03): : 252 - 260
  • [27] EFFECTS OF INTENSIVE DIETARY-TREATMENT ON INSULIN-STIMULATED SKELETAL-MUSCLE GLYCOGEN-SYNTHASE ACTIVATION AND INSULIN-SECRETION IN NEWLY PRESENTING TYPE-2 DIABETIC-PATIENTS
    JOHNSON, AB
    ARGYRAKI, M
    THOW, JC
    BROUGHTON, D
    JONES, IR
    TAYLOR, R
    [J]. DIABETIC MEDICINE, 1990, 7 (05) : 420 - 428
  • [28] ISOZYMES OF GLYCOGEN-SYNTHASE
    KASLOW, HR
    LESIKAR, DD
    [J]. FEBS LETTERS, 1984, 172 (02): : 294 - 298
  • [29] BASAL AND INSULIN-MEDIATED CARBOHYDRATE-METABOLISM IN HUMAN MUSCLE DEFICIENT IN PHOSPHOFRUCTOKINASE-1
    KATZ, A
    SPENCER, MK
    LILLIOJA, S
    YAN, Z
    MOTT, DM
    HALLER, RG
    LEWIS, SF
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (04): : E473 - E478
  • [30] HYPERGLYCEMIA NORMALIZES INSULIN-STIMULATED SKELETAL-MUSCLE GLUCOSE-OXIDATION AND STORAGE IN NONINSULIN-DEPENDENT DIABETES-MELLITUS
    KELLEY, DE
    MANDARINO, LJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (06) : 1999 - 2007