An overview of pancreatic beta-cell defects in human type 2 diabetes: Implications for treatment

被引:87
作者
Marchetti, Piero [1 ,2 ]
Dotta, Francesco [3 ]
Lauro, Davide [4 ]
Purrello, Francesco [5 ]
机构
[1] Cisanello Hosp, Dept Endocrinol & Metab, Metab Unit, I-56100 Pisa, Italy
[2] Univ Pisa, Dept Endocrinol & Metab, Metab Unit, Pisa, Italy
[3] Univ Siena, Dept Internal Med, I-53100 Siena, Italy
[4] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy
[5] Univ Catania, Dept Internal Med, Catania, Italy
关键词
type; 2; diabetes; pancreatic beta-cell; insulin secretion; apoptosis;
D O I
10.1016/j.regpep.2007.08.017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Type 2 diabetes is the most common form of diabetes in humans. It results from a combination of factors that impair beta-cell function and tissue insulin sensitivity. However, growing evidence is showing that the beta-cell is central to the development and progression of this form of diabetes. Reduced islet and/or insulin-containing cell mass or volume in Type 2 diabetes has been reported by several authors. Furthermore, studies with isolated Type 2 diabetic islets have consistently shown both quantitative and qualitative defects of glucose-stimulated insulin secretion. The impact of genotype in affecting beta-cell function and survival is a very fast growing field or research, and several gene polymorphisms have been associated with this form of diabetes. Among acquired factors, glucotoxicity, lipotoxicity and altered IAPP processing are likely to play an important role. Interestingly, however, pharmacological intervention can improve several defects of Type 2 diabetes islet cells in vitro, suggesting that progression of the disease might not be relentless. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:4 / 11
页数:8
相关论文
共 66 条
[1]  
AHREN B, 2004, HORM METAB RES, V36, P775
[2]  
*AM DIAB ASS, 2001, DIABETES VITAL STAT, P5
[3]  
*AM DIAB ASS, 2001, DIAB 2001 VIT STAT, P75
[4]  
Am Diabetes Assoc, 2006, DIABETES CARE, V29, pS4
[5]   Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic β-cells [J].
Andreozzi, F ;
D'Alessandris, C ;
Federici, M ;
Laratta, E ;
Del Guerra, S ;
Del Prato, S ;
Marchetti, P ;
Lauro, R ;
Perticone, F ;
Sesti, G .
ENDOCRINOLOGY, 2004, 145 (06) :2845-2857
[6]   Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients [J].
Anello, M ;
Lupi, R ;
Spampinato, D ;
Piro, S ;
Masini, M ;
Boggi, U ;
Del Prato, S ;
Rabuazzo, AM ;
Purrello, F ;
Marchetti, P .
DIABETOLOGIA, 2005, 48 (02) :282-289
[7]   Diabetes mellitus and genetically programmed defects in β-cell function [J].
Bell, GI ;
Polonsky, KS .
NATURE, 2001, 414 (6865) :788-791
[8]   New sources of pancreatic β-cells [J].
Bonner-Weir, S ;
Weir, GC .
NATURE BIOTECHNOLOGY, 2005, 23 (07) :857-861
[9]  
Buchanan L, 2003, INC, V25, P46
[10]   β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes [J].
Butler, AE ;
Janson, J ;
Bonner-Weir, S ;
Ritzel, R ;
Rizza, RA ;
Butler, PC .
DIABETES, 2003, 52 (01) :102-110