IMPAIRED NET HEPATIC GLYCOGEN-SYNTHESIS IN INSULIN-DEPENDENT DIABETIC SUBJECTS DURING MIXED MEAL INGESTION - A C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDY

被引:158
作者
HWANG, JH [1 ]
PERSEGHIN, G [1 ]
ROTHMAN, DL [1 ]
CLINE, GW [1 ]
MAGNUSSON, I [1 ]
PETERSEN, KF [1 ]
SHULMAN, GI [1 ]
机构
[1] YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06520
关键词
GLYCOGENOLYSIS; GLUCONEOGENESIS; NMR SPECTROSCOPY; DIABETES MELLITUS;
D O I
10.1172/JCI117727
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
Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using C-13 nuclear magnetic resonance spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units --> --> glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-C-13]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia.
引用
收藏
页码:783 / 787
页数:5
相关论文
共 23 条
[1]  
BARZILAI N, 1993, J BIOL CHEM, V268, P25019
[2]   PORTAL AND PERIPHERAL VEIN IMMUNOREACTIVE GLUCAGON CONCENTRATIONS AFTER ARGININE OR GLUCOSE INFUSIONS [J].
BLACKARD, WG ;
NELSON, NC ;
ANDREWS, SS .
DIABETES, 1974, 23 (03) :199-202
[3]   DIFFERENTIAL TIME COURSE OF GLUCAGONS EFFECT ON GLYCOGENOLYSIS AND GLUCONEOGENESIS IN THE CONSCIOUS DOG [J].
CHERRINGTON, AD ;
WILLIAMS, PE ;
SHULMAN, GI ;
LACY, WW .
DIABETES, 1981, 30 (03) :180-187
[4]   DIFFERENTIAL SENSITIVITY OF GLYCOGENOLYSIS AND GLUCONEOGENESIS TO INSULIN INFUSIONS IN DOGS [J].
CHIASSON, JL ;
LILJENQUIST, JE ;
FINGER, FE ;
LACY, WW .
DIABETES, 1976, 25 (04) :283-291
[5]   HYPOGLYCEMIA IN IDDM [J].
CRYER, PE ;
BINDER, C ;
BOLLI, GB ;
CHERRINGTON, AD ;
GALE, EAM ;
GERICH, JE ;
SHERWIN, RS .
DIABETES, 1989, 38 (09) :1193-1199
[6]   SUPPRESSION OF SLEEP-INDUCED GROWTH-HORMONE SECRETION BY ANTICHOLINERGIC AGENT ABOLISHES DAWN PHENOMENON [J].
DAVIDSON, MB ;
HARRIS, MD ;
ZIEL, FH ;
ROSENBERG, CS .
DIABETES, 1988, 37 (02) :166-171
[7]   PATHOGENESIS OF NIDDM - A BALANCED OVERVIEW [J].
DEFRONZO, RA ;
BONADONNA, RC ;
FERRANNINI, E .
DIABETES CARE, 1992, 15 (03) :318-368
[8]   FLASH IMAGING - RAPID NMR IMAGING USING LOW FLIP-ANGLE PULSES [J].
HAASE, A ;
FRAHM, J ;
MATTHAEI, D ;
HANICKE, W ;
MERBOLDT, KD .
JOURNAL OF MAGNETIC RESONANCE, 1986, 67 (02) :258-266
[9]   CONTRIBUTION OF HEPATIC GLYCOGENOLYSIS TO GLUCOSE-PRODUCTION IN HUMANS IN RESPONSE TO A PHYSIOLOGICAL INCREASE IN PLASMA-GLUCAGON CONCENTRATION [J].
MAGNUSSON, I ;
ROTHMAN, DL ;
GERARD, DP ;
KATZ, LD ;
SHULMAN, GI .
DIABETES, 1995, 44 (02) :185-189
[10]   INCREASED RATE OF GLUCONEOGENESIS IN TYPE-II DIABETES-MELLITUS - A C-13 NUCLEAR-MAGNETIC-RESONANCE STUDY [J].
MAGNUSSON, I ;
ROTHMAN, DL ;
KATZ, LD ;
SHULMAN, RG ;
SHULMAN, GI .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (04) :1323-1327