The roles of insulin and glucagon in the regulation of hepatic glycogen synthesis and turnover in humans

被引:129
作者
Roden, M [1 ]
Perseghin, G [1 ]
Petersen, KF [1 ]
Hwang, JH [1 ]
Cline, GW [1 ]
Gerow, K [1 ]
Rothman, DL [1 ]
Shulman, GI [1 ]
机构
[1] YALE UNIV, SCH MED, DEPT INTERNAL MED, NEW HAVEN, CT 06520 USA
关键词
gluconeogenesis; somatostatin; acetaminophen C-13 NMR spectroscopy;
D O I
10.1172/JCI118460
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
To determine the respective roles of insulin and glucagon for hepatic glycogen synthesis and turnover, hyperglycemic clamps were performed with somatostatin [0.1 mu g(kg . min)] in healthy young men under conditions of (I) basal (fasting) portal vein insulinemia-hypoglucagonemia, (II) basal portal vein insulinemia-basal glucagonemia, and (III) basal peripheral insulinemia-hypoglucagonemia. Synthetic rates. pathway (direct versus indirect) contributions, and percent turnover of hepatic glycogen were assessed by in vivo C-13 nuclear magnetic resonance spectroscopy during [1-C-13]glucose infusion follow ed by a natural abundance glucose chase in conjunction with acetaminophen to noninvasiv ely sample the hepatic UDP-glucose pool. In the presence of hyperglycemia (10.4+/-0.1 mM) and basal portal vein insulinemia (192+/-6 pM), suppression of glucagon secretion (plasma glucagon, I: 31+/-4, II: 63+/-8 pg/ml) doubled the hepatic accumulation of glycogen (V-syn) compared with conditions of basal glucagonemia [I: 0.40+/-0.06, II: 0.19+/-0.03 mmol/(liter . min); P < 0.0025]. Glycogen turnover was markedly reduced (I: 19=7% II: 69+/-12%; P < 0.005), so that net rate of glycogen synthesis increased approximately fivefold (P < 0.001) by inhibition of glucagon secretion. The relative contribution of gluconeogenesis (indirect pathway) to glycogen synthesis was lower during hypoglucagonemia (42+/-6%) than during basal glucagonemia (54+/-5%; P < 0.005). Under conditions of basal peripheral insulinemia (54+/-12 pM) and hypo,glucagonemia (III) there was negligible hepatic glycogen synthesis and turnover. In conclusion, small changes in portal vein concentrations of insulin and glucagon independently affect hepatic glycogen synthesis and turnover. Inhibition of glucagon secretion under conditions of hyperglycemia and basal concentrations of insulin results in: (a) twofold increase in rate of hepatic glycogen synthesis, (b) reduction of glycogen turnover by similar to 73%, and (c) augmented percent contribution of the direct pathway to glycogen synthesis compared with conditions of basal glucagonemia.
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页码:642 / 648
页数:7
相关论文
共 48 条
[1]   PORTAL AND PERIPHERAL VEIN IMMUNOREACTIVE INSULIN CONCENTRATIONS BEFORE AND AFTER GLUCOSE INFUSION [J].
BLACKARD, WG ;
NELSON, NC .
DIABETES, 1970, 19 (05) :302-&
[2]   GLUCONEOGENESIS FROM ALANINE IN NORMAL POSTABSORPTIVE MAN - INTRAHEPATIC STIMULATORY EFFECT OF GLUCAGON [J].
CHIASSON, JL ;
LILJENQUIST, JE ;
SINCLAIRSMITH, BC ;
LACY, WW .
DIABETES, 1975, 24 (06) :574-584
[3]   24-HOUR STUDIES OF EFFECTS OF SOMATOSTATIN ON LEVELS OF PLASMA GROWTH-HORMONE, GLUCAGON, AND GLUCOSE IN NORMAL SUBJECTS AND JUVENILE DIABETICS [J].
CHRISTENSEN, SE ;
HANSEN, AP ;
WEEKE, J ;
LUNDBAEK, K .
DIABETES, 1978, 27 (03) :300-306
[4]   C-13-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY STUDIES OF HEPATIC GLUCOSE-METABOLISM IN NORMAL SUBJECTS AND SUBJECTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS [J].
CLINE, GW ;
ROTHMAN, DL ;
MAGNUSSON, I ;
KATZ, LD ;
SHULMAN, GI .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (06) :2369-2376
[5]   REGULATION OF SPLANCHNIC AND PERIPHERAL GLUCOSE-UPTAKE BY INSULIN AND HYPERGLYCEMIA IN MAN [J].
DEFRONZO, RA ;
FERRANNINI, E ;
HENDLER, R ;
FELIG, P ;
WAHREN, J .
DIABETES, 1983, 32 (01) :35-45
[6]  
DEFRONZO RA, 1979, AM J PHYSIOL, V237, pE214
[7]   EFFECTS OF A LONG-ACTING SOMATOSTATIN ANALOG ON POSTPRANDIAL HYPERGLYCEMIA IN INSULIN-DEPENDENT DIABETES-MELLITUS [J].
DIMITRIADIS, G ;
TESSARI, P ;
GERICH, J .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1983, 32 (10) :987-992
[8]   FAILURE OF GLUCAGON SUPPRESSION CONTRIBUTES TO POSTPRANDIAL HYPERGLYCEMIA IN IDDM [J].
DINNEEN, S ;
ALZAID, A ;
TURK, D ;
RIZZA, R .
DIABETOLOGIA, 1995, 38 (03) :337-343
[9]   METABOLIC EFFECTS OF THE NOCTURNAL RISE IN CORTISOL ON CARBOHYDRATE-METABOLISM IN NORMAL HUMANS [J].
DINNEEN, S ;
ALZAID, A ;
MILES, J ;
RIZZA, R .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (05) :2283-2290
[10]  
EXTON JH, 1967, J BIOL CHEM, V242, P2622