Beta-cell activity and destruction in type 1 diabetes

被引:21
作者
Karlsson, FA [1 ]
Berne, C [1 ]
Björk, E [1 ]
Kullin, M [1 ]
Li, ZC [1 ]
Ma, JY [1 ]
Schölin, A [1 ]
Zhao, LJ [1 ]
机构
[1] Univ Uppsala Hosp, Dept Med Sci, S-75185 Uppsala, Sweden
关键词
D O I
10.1517/03009734000000056
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Type 1 diabetes is the result of a chronic inflammatory process that causes elimination of insulin-producing beta-cells, resulting in insulin deficiency and hyperglycemia . The destruction is thought to be mediated by an autoimmune process involving cytotoxic T cells recognizing beta-cell autoantigens in the context of MHC class I-peptide complexes. Autoantibodies against insulin, glutamic acid decarboxylase (CAD) and and ICA 512 protein tyrosine phosphatase are frequently found. At the clinical onset of diabetes, some beta-cells remain and after initiation of insulin treatment, most patients enter a period of remission, a phenomenon that may reflect diminished autoimmune activity in the islets. There is evidence to suggest that a further loss of beta-cells can be curtailed, and that patients, who maintain endogenous insulin production, have better glycemic control and less risk of complications. This is the basis for our current research. We are characterizing the remission phenomenon in epidemiological studies in order to identify determinants of beta-cell survival. In randomized, prospective multicenter trials, we are evaluating the benefit of beta-cell secretory rest for rescue of insulin production in patients at onset of clinical disease. In experimental studies, we are investigating expression and regulation of the key molecules of an autoimmune process in the islets. Further, selective beta-cell damage is induced in rat islets and measures to enhance beta-cell resistance and repair are being examined. We have recently identified a remarkable, beta-cell protective effect of K-ATP-channel opening.
引用
收藏
页码:85 / 95
页数:11
相关论文
共 52 条
[21]   Direct effects of diazoxide on mitochondria in pancreatic B-cells and on isolated liver mitochondria [J].
Grimmsmann, T ;
Rustenbeck, I .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (05) :781-788
[22]  
GROVER GJ, 1991, J PHARMACOL EXP THER, V257, P156
[23]   REGULATION OF GLUTAMIC-ACID DECARBOXYLASE DIABETES AUTOANTIGEN EXPRESSION IN HIGHLY PURIFIED ISOLATED ISLETS FROM MACACA-NEMESTRINA [J].
HAGOPIAN, WA ;
KARLSEN, AE ;
PETERSEN, JS ;
TEAGUE, J ;
GERVASSI, A ;
JIANG, JJ ;
FUJIMOTO, W ;
LERNMARK, A .
ENDOCRINOLOGY, 1993, 132 (06) :2674-2681
[24]   MACROPHAGES, T-CELL RECEPTOR USAGE, AND ENDOTHELIAL-CELL ACTIVATION IN THE PANCREAS AT THE ONSET OF INSULIN-DEPENDENT DIABETES-MELLITUS [J].
HANNINEN, A ;
JALKANEN, S ;
SALMI, M ;
TOIKKANEN, S ;
NIKOLAKAROS, G ;
SIMELL, O .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (05) :1901-1910
[25]   EVIDENCE OF BETA-CELL DYSFUNCTION WHICH DOES NOT LEAD ON TO DIABETES - A STUDY OF IDENTICAL-TWINS OF INSULIN-DEPENDENT DIABETICS [J].
HEATON, DA ;
MILLWARD, BA ;
GRAY, P ;
TUN, Y ;
HALES, CN ;
PYKE, DA ;
LESLIE, RDG .
BRITISH MEDICAL JOURNAL, 1987, 294 (6565) :145-146
[26]   OPPOSITE EFFECTS OF TOLBUTAMIDE AND DIAZOXIDE ON RB-86+ FLUXES AND MEMBRANE-POTENTIAL IN PANCREATIC B-CELLS [J].
HENQUIN, JC ;
MEISSNER, HP .
BIOCHEMICAL PHARMACOLOGY, 1982, 31 (07) :1407-1415
[27]   SIGNALS AND SIGNS FOR LYMPHOCYTE-RESPONSES [J].
JANEWAY, CA ;
BOTTOMLY, K .
CELL, 1994, 76 (02) :275-285
[28]   HIGH-GLUCOSE STIMULATION OF 64,000-MR ISLET CELL AUTO-ANTIGEN EXPRESSION [J].
KAMPE, O ;
ANDERSSON, A ;
BJORK, E ;
HALLBERG, A ;
KARLSSON, FA .
DIABETES, 1989, 38 (10) :1326-1328
[29]   MAJOR PARIETAL-CELL ANTIGEN IN AUTOIMMUNE GASTRITIS WITH PERNICIOUS-ANEMIA IS THE ACID-PRODUCING H+,K+-ADENOSINE TRIPHOSPHATASE OF THE STOMACH [J].
KARLSSON, FA ;
BURMAN, P ;
LOOF, L ;
MARDH, S .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (02) :475-479
[30]   Beta-cell rest: A strategy for the prevention of autoimmune diabetes [J].
Karlsson, FA ;
Bjork, E .
AUTOIMMUNITY, 1997, 26 (02) :117-122