Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients

被引:111
作者
Gastaldelli, A
Toschi, E
Pettiti, M
Frascerra, S
Quiñones-Galvan, A
Sironi, AM
Natali, A
Ferrannini, E
机构
[1] CNR, Inst Clin Physiol, Metab Unit, I-56100 Pisa, Italy
[2] Univ Pisa, Sch Med, Dept Internal Med, I-56100 Pisa, Italy
关键词
D O I
10.2337/diabetes.50.8.1807
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Gluconeogenesis (GNG) is enhanced in type 2 diabetes. In experimental animals, insulin at high doses decreases the incorporation of labeled GNG precursors into plasma glucose. Whether physiological hyperinsulinemia has any effect on total GNG in humans has not been determined. We combined the insulin clamp with the (H2O)-H-2 technique to measure total GNG in 33 subjects with type 2 diabetes (BMI 29.0 +/- 0.6 kg/m(2), fasting plasma glucose 8.1 +/- 0.3 mmol/l) and in 9 nondiabetic BMI-matched subjects after 16 h of fasting and after euglycemic hyperinsulinemia. A primed-constant infusion of 6,6-H-2-glucose was used to monitor endogenous glucose output (EGO); insulin (40 mU.min(-1).m(-2)) was then infused while clamping plasma glucose for 2 h (at 5.8 +/- 0.1 and 4.9 +/- 0.2 mmol/l for diabetic and control subjects, respectively). In the fasting state, EGO averaged 15.2 +/- 0.4 mu mol.min(-1).kg(ffm)(-1) (62% from GNG) in diabetic subjects and 12.2 +/- 0.7 mu mol.min(-1).kg(ffm)(-1) (55% from GNG) in control subjects (P < 0.05 or less for both fluxes). Glycogenolysis (EGO - GNG) was similar in the two groups (P = NS). During the last 40 min of the clamp, both EGO and GNG were significantly (P < 0.01 or less, compared with fasting) inhibited (EGO 7.1 +/- 0.9 and 3.6 +/- 0.5 and GNG 7.9 +/- 0.5 and 4.5 +/- 1.0 mu mol.min(-1).kg(ffm)(-1) in diabetic and control subjects, respectively) but remained significantly (P < 0.05) higher in diabetic subjects, whereas glycogenolysis was suppressed completely and equally in both groups. During hyperinsulinemia, GNG was reciprocally related to plasma glucose clearance. In conclusion, physiological hyperinsulinemia suppresses GNG by similar to 20%, while completely blocking glycogenolysis. Resistance of GNG (to insulin suppression) and resistance of glucose uptake (to insulin stimulation) are coupled phenomena. In type 2 diabetes, the excess GNG of the fasting state is carried over to the insulinized state, thereby contributing to glucose overproduction under both conditions.
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页码:1807 / 1812
页数:6
相关论文
共 24 条
  • [1] Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism - Evidence for a defect in haptic glucokinase activity
    Basu, A
    Basu, R
    Shah, P
    Vella, A
    Johnson, CM
    Nair, KS
    Jensen, MD
    Schwenk, WF
    Rizza, RA
    [J]. DIABETES, 2000, 49 (02) : 272 - 283
  • [2] Quantification of gluconeogenesis in cirrhosis: Response to glucagon
    Bugianesi, E
    Kalhan, S
    Burkett, E
    Marchesini, G
    McCullough, A
    [J]. GASTROENTEROLOGY, 1998, 115 (06) : 1530 - 1540
  • [3] Regulation of splanchnic and renal substrate supply by insulin in humans
    Cersosimo, E
    Garlick, P
    Ferretti, J
    [J]. METABOLISM-CLINICAL AND EXPERIMENTAL, 2000, 49 (05): : 676 - 683
  • [4] Quantifying gluconeogenesis during fasting
    Chandramouli, V
    Ekberg, K
    Schumann, WC
    Kalhan, SC
    Wahren, J
    Landau, BR
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1997, 273 (06): : E1209 - E1215
  • [5] The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects
    Chen, XH
    Iqbal, N
    Boden, G
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (03) : 365 - 372
  • [6] Control of glucose uptake and release by the liver in vivo
    Cherrington, AD
    [J]. DIABETES, 1999, 48 (05) : 1198 - 1214
  • [7] DIFFERENTIAL SENSITIVITY OF GLYCOGENOLYSIS AND GLUCONEOGENESIS TO INSULIN INFUSIONS IN DOGS
    CHIASSON, JL
    LILJENQUIST, JE
    FINGER, FE
    LACY, WW
    [J]. DIABETES, 1976, 25 (04) : 283 - 291
  • [8] MILD TYPE-2 DIABETES MARKEDLY INCREASES GLUCOSE CYCLING IN THE POSTABSORPTIVE STATE AND DURING GLUCOSE-INFUSION IRRESPECTIVE OF OBESITY
    EFENDIC, S
    KARLANDER, S
    VRANIC, M
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (06) : 1953 - 1961
  • [9] Ferrannini EDS, 1986, METHODS DIABETES RES, VII, P107
  • [10] Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans - A quantitative study
    Gastaldelli, A
    Baldi, S
    Pettiti, M
    Toschi, E
    Camastra, S
    Natali, A
    Landau, BR
    Ferrannini, E
    [J]. DIABETES, 2000, 49 (08) : 1367 - 1373