The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus

被引:460
作者
Pratley, RE [1 ]
Weyer, C [1 ]
机构
[1] NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA
关键词
insulin action; insulin secretion; Type II diabetes mellitus; impaired glucose tolerance; pathogenesis;
D O I
10.1007/s001250100580
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Patients with Type II (non-insulin-dependent) diabetes mellitus manifest abnormalities in insulin action and insulin secretion. It is widely accepted that insulin resistance is an early finding, evident before the onset of hyperglycaemia and predictive of the subsequent development of diabetes. Whether abnormalities in insulin secretion also precede and predict diabetes has been debated. However, recent studies clearly indicate that early insulin secretion plays a critical role in maintaining normal glucose homeostasis. Cross-sectional analyses show that acute insulin secretory responses (Ally) to intravenous glucose are lower in subjects with impaired glucose tolerance and those at high risk for developing diabetes. Prospectively, a low AIR predicts the development of diabetes in several populations. In longitudinal studies, AIR declines dramatically as patients progress from normal to impaired glucose tolerance and ultimately to diabetes. Early insulin secretion is important for the rapid and efficient suppression of endogenous glucose production after a meal. Thus, loss of early insulin secretion initially leads to post-prandial hyperglycaemia which, as the disease progresses, worsens to clinical hyperglycaemia. Strategies that enhance early insulin secretion improve glucose tolerance and represent a novel and more physiologic approach to improving glycaemic control in patients with Type II diabetes mellitus.
引用
收藏
页码:929 / 945
页数:17
相关论文
共 98 条
[1]   THE DIABETIC INTRAUTERINE MILIEU HAS A LONG-LASTING EFFECT ON INSULIN-SECRETION BY B-CELLS AND ON INSULIN UPTAKE BY TARGET TISSUES [J].
AERTS, L ;
SODOYEZGOFFAUX, F ;
SODOYEZ, JC ;
MALAISSE, WJ ;
VANASSCHE, FA .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1988, 159 (05) :1287-1292
[2]   MATERNAL DIABETES DURING PREGNANCY - CONSEQUENCES FOR THE OFFSPRING [J].
AERTS, L ;
HOLEMANS, K ;
VANASSCHE, FA .
DIABETES-METABOLISM REVIEWS, 1990, 6 (03) :147-167
[3]  
Bergman RN, 1997, RECENT PROG HORM RES, V52, P359
[4]   RELATIONSHIP BETWEEN GLUCOSE-TOLERANCE AND GLUCOSE-STIMULATED INSULIN-RESPONSE IN 65-YEAR-OLDS [J].
BOUREY, RE ;
KOHRT, WM ;
KIRWAN, JP ;
STATEN, MA ;
KING, DS ;
HOLLOSZY, JO .
JOURNALS OF GERONTOLOGY, 1993, 48 (04) :M122-M127
[5]   PHYSIOLOGICAL IMPORTANCE OF DEFICIENCY IN EARLY PRANDIAL INSULIN-SECRETION IN NON-INSULIN-DEPENDENT DIABETES [J].
BRUCE, DG ;
CHISHOLM, DJ ;
STORLIEN, LH ;
KRAEGEN, EW .
DIABETES, 1988, 37 (06) :736-744
[6]   RELATIONSHIPS BETWEEN FASTING PLASMA GLUCOSE LEVELS AND INSULIN-SECRETION DURING INTRAVENOUS GLUCOSE-TOLERANCE TESTS [J].
BRUNZELL, JD ;
ROBERTSON, RP ;
LERNER, RL ;
HAZZARD, WR ;
ENSINCK, JW ;
BIERMAN, EL ;
PORTE, D .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1976, 42 (02) :222-229
[7]   Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients [J].
Bruttomesso, D ;
Pianta, A ;
Mari, A ;
Valerio, A ;
Marescotti, MC ;
Avogaro, A ;
Tiengo, A ;
Del Prato, S .
DIABETES, 1999, 48 (01) :99-105
[8]  
BRYNE MM, 2000, DIABETES MELLITUS FU, P105
[9]   LOSS OF EARLY PHASE OF INSULIN RELEASE IN HUMANS IMPAIRS GLUCOSE-TOLERANCE AND BLUNTS THERMAL EFFECT OF GLUCOSE [J].
CALLESESCANDON, J ;
ROBBINS, DC .
DIABETES, 1987, 36 (10) :1167-1172
[10]   INTERSTITIAL INSULIN CONCENTRATIONS DETERMINE GLUCOSE-UPTAKE RATES BUT NOT INSULIN-RESISTANCE IN LEAN AND OBESE MEN [J].
CASTILLO, C ;
BOGARDUS, C ;
BERGMAN, R ;
THUILLEZ, P ;
LILLIOJA, S .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (01) :10-16