Beta-cell adaptation and decompensation during the progression of diabetes.

Abstract:

:Inadequate beta-cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta-cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS). This review discusses the ways in which beta-cells successfully adapt to increased demand and then decompensate as diabetes develops. Successful adaptation is achieved through increased beta-cell mass and increased insulin secretion. The hypothesis is explored that beta-cells exposed to the diabetic milieu lose their differentiation, which leads to loss of specialized functions such as GIIS. This concept has been strengthened by the finding of dedifferentiation of beta-cells in a rat model of partial pancreatectomy that includes a reduction of insulin gene expression, which may further contribute to decreased insulin production. Another finding was increased expression of c-Myc, which probably contributes to an increase in the expression of lactate dehydrogenase and the development of beta-cell hypertrophy. Arguments are developed that the beta-cell changes found in diabetes are better correlated with increased glucose levels than with non-esterified fatty acid levels, thus supporting the importance of glucose toxicity.

journal_name

Diabetes

journal_title

Diabetes

authors

Weir GC,Laybutt DR,Kaneto H,Bonner-Weir S,Sharma A

doi

10.2337/diabetes.50.2007.s154

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

S154-9

eissn

0012-1797

issn

1939-327X

journal_volume

50 Suppl 1

pub_type

杂志文章,评审

相关文献

DIABETES文献大全
  • Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome.

    abstract::The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cho...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.8.2087

    authors: Carr DB,Utzschneider KM,Hull RL,Kodama K,Retzlaff BM,Brunzell JD,Shofer JB,Fish BE,Knopp RH,Kahn SE

    更新日期:2004-08-01 00:00:00

  • Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat.

    abstract::Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.12.2222

    authors: Collison M,Glazier AM,Graham D,Morton JJ,Dominiczak MH,Aitman TJ,Connell JM,Gould GW,Dominiczak AF

    更新日期:2000-12-01 00:00:00

  • Changes in the dimeric state of neuronal nitric oxide synthase affect the kinetics of secretagogue-induced insulin response.

    abstract::We previously showed that pancreatic beta-cells express a neuronal isoform of nitric oxide synthase (nNOS) that controls insulin secretion by exerting two enzymatic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now bring evidence that two inhibitors of nNOS, N-omega-nitro-l-arginine ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.6.1467

    authors: Lajoix AD,Pugnière M,Roquet F,Mani JC,Dietz S,Linck N,Faurie F,Ribes G,Petit P,Gross R

    更新日期:2004-06-01 00:00:00

  • Prevention of recurrence of IDDM in islet-transplanted diabetic NOD mice by adjuvant immunotherapy.

    abstract::Insulin-dependent diabetes mellitus (IDDM) involves the destruction of the insulin-producing cells in the islets of Langerhans. One possible cure is by transplanting the islet cells; however, transplanted islets, even between identical twins, are subject to autoimmune destruction by the disease process, resulting in d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.1.114

    authors: Wang T,Singh B,Warnock GL,Rajotte RV

    更新日期:1992-01-01 00:00:00

  • Cellular Origins of Beige Fat Cells Revisited.

    abstract::Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precursors or through reprogramming of mature white adipocytes has been...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0308

    authors: Shao M,Wang QA,Song A,Vishvanath L,Busbuso NC,Scherer PE,Gupta RK

    更新日期:2019-10-01 00:00:00

  • Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas.

    abstract::The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1187

    authors: Ait-Lounis A,Baas D,Barras E,Benadiba C,Charollais A,Nlend Nlend R,Liègeois D,Meda P,Durand B,Reith W

    更新日期:2007-04-01 00:00:00

  • PTPN22 silencing in the NOD model indicates the type 1 diabetes-associated allele is not a loss-of-function variant.

    abstract::PTPN22 encodes the lymphoid tyrosine phosphatase (LYP) and is the second strongest non-HLA genetic risk factor for type 1 diabetes. The PTPN22 susceptibility allele generates an LYP variant with an arginine-to-tryptophan substitution at position 620 (R620W) that has been reported by several studies to impart a gain of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0929

    authors: Zheng P,Kissler S

    更新日期:2013-03-01 00:00:00

  • New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients.

    abstract::Effects of oral administration of DG-5128, a new oral hypoglycemic agent, on glycemic control after a mixed meal and an in vivo glucose disposal were measured in subjects with nonobese non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of DG-5128 significantly (P less than .05) enhanced insulin secre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.10.1085

    authors: Kashiwagi A,Harano Y,Suzuki M,Kojima H,Harada M,Nishio Y,Shigeta Y

    更新日期:1986-10-01 00:00:00

  • Quantification of collagen in renal glomeruli isolated from human nondiabetic and diabetic kidneys.

    abstract::Previous studies of diabetic renovascular complications have measured morphologic changes in relatively few glomerular vessels by electron microscopy. The present study samples 20,000 to 80,000 glomeruli from each of ten nondiabetic and ten diabetic age- and sex-matched subjects. Glomeruli were isolated and fractionat...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.12.1057

    authors: Klein L,Butcher DL,Sudilovsky O,Kikkawa R,Miller M

    更新日期:1975-12-01 00:00:00

  • Biosynthesis of proinsulin and other islet cell proteins in pancreatic beta cells of the rat: a radioautographic evaluation of glucose effects in vitro.

    abstract::Rat pancreatic islets were incubated in vitro with L-[4,5-3H]leucine or with L-[2,3-3H]tryptophan in Krebs-Ringer bicarbonate buffer, containing 0, 5, or 20 mM glucose. Incorporation of labeled amino acids in islet cells was evaluated quantitatively by a validated radioautographic procedure. Incorporation of labeled l...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diacare.20.10.795

    authors: Logothetopoulos J,Jain K

    更新日期:1980-10-01 00:00:00

  • DLL1- and DLL4-Mediated Notch Signaling Is Essential for Adult Pancreatic Islet Homeostasis.

    abstract::Genes of the Notch signaling pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. The Notch ligand Delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of multipotent progenitors in the developing pancreas, and loss of D...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0795

    authors: Rubey M,Chhabra NF,Gradinger D,Sanz-Moreno A,Lickert H,Przemeck GKH,Hrabě de Angelis M

    更新日期:2020-05-01 00:00:00

  • Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance.

    abstract:OBJECTIVE:We examined the relationship between the expression of thrombospondin (TSP)1, an antiangiogenic factor and regulator of transforming growth factor-beta activity, obesity, adipose inflammation, and insulin resistance. RESEARCH DESIGN AND METHODS:TSP1 gene expression was quantified in subcutaneous adipose tiss...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0840

    authors: Varma V,Yao-Borengasser A,Bodles AM,Rasouli N,Phanavanh B,Nolen GT,Kern EM,Nagarajan R,Spencer HJ 3rd,Lee MJ,Fried SK,McGehee RE Jr,Peterson CA,Kern PA

    更新日期:2008-02-01 00:00:00

  • Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats.

    abstract::Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotoci...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1042

    authors: Kim YB,Kim WB,Jung WW,Jin X,Kim YS,Kim B,Han HC,Block GD,Colwell CS,Kim YI

    更新日期:2018-03-01 00:00:00

  • Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.

    abstract::The sustained expression of the MAFB transcription factor in human islet β-cells represents a distinct difference in mice. Moreover, mRNA expression of closely related and islet β-cell-enriched MAFA does not peak in humans until after 9 years of age. We show that the MAFA protein also is weakly produced within the juv...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0903

    authors: Cyphert HA,Walker EM,Hang Y,Dhawan S,Haliyur R,Bonatakis L,Avrahami D,Brissova M,Kaestner KH,Bhushan A,Powers AC,Stein R

    更新日期:2019-02-01 00:00:00

  • Diabetes in pregnancy. Skeletal malformations in the offspring of diabetic rats after intermittent withdrawal of insulin in early gestation.

    abstract::Precise timing of the teratogenic period in diabetic pregnancy is of clinical importance since correction of the glucose intolerance during this period may protect the offspring from malformations. An experimental approach to elucidate this problem with regard to skeletal development was made in groups of pregnant str...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.12.1141

    authors: Eriksson UJ,Dahlström E,Hellerström C

    更新日期:1983-12-01 00:00:00

  • Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes.

    abstract::A simple, direct assay for T-lymphocyte reactivity to islet antigen(s) in human insulin-dependent diabetes mellitus (IDDM) should facilitate preclinical diagnosis and the evaluation of intervention therapy to avert autoimmune-mediated beta-cell destruction. In subjects with preclinical or clinical IDDM, we measured th...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.9.1128

    authors: Harrison LC,De Aizpurua H,Loudovaris T,Campbell IL,Cebon JS,Tait BD,Colman PG

    更新日期:1991-09-01 00:00:00

  • Persistence of serum antibodies to 64,000-Mr islet cell protein after onset of type I diabetes.

    abstract::Antibodies to an islet protein of 64,000 Mr (64K antibodies) were measured in 15 diabetic children who were followed prospectively for up to 3 yr after onset of type I (insulin-dependent) diabetes. Of the 15 children, 12 were positive for 64K antibodies at diagnosis. Those patients who were negative for these antibodi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.39.6.653

    authors: Christie MR,Daneman D,Champagne P,Delovitch TL

    更新日期:1990-06-01 00:00:00

  • Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes.

    abstract:OBJECTIVE:12/15-lipoxygenase (12/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to produce proinflammatory lipids. 12/15-LO is expressed in macrophages and pancreatic beta-cells. It enhances interleukin 12 production by macrophages, and several of its products induce apo...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0830

    authors: McDuffie M,Maybee NA,Keller SR,Stevens BK,Garmey JC,Morris MA,Kropf E,Rival C,Ma K,Carter JD,Tersey SA,Nunemaker CS,Nadler JL

    更新日期:2008-01-01 00:00:00

  • The mechanism of action of insulin on phospholipid metabolism in rat adipose tissue. Requirement for protein synthesis and a carbohydrate source, and relationship to activation of pyruvate dehydrogenase.

    abstract::We studied certain metabolic requirements for insulin-induced increases in phospholipids, and the relationship of phospholipid changes to the insulin-induced activation of pyruvate dehydrogenase, in rat adipocytes and fat pads in vitro. Increases in the contents of phosphatidylinositol and phosphatidylserine mass were...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.7.648

    authors: Farese RV,Farese RV Jr,Sabir MA,Larson RE,Trudeau WL 3rd,Barnes D

    更新日期:1984-07-01 00:00:00

  • Prediction of metabolic syndrome by low serum testosterone levels in men: results from the study of health in Pomerania.

    abstract:OBJECTIVE:The aim of this analysis was to assess the prospective association of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with incident metabolic syndrome (MetS) in men. RESEARCH DESIGN AND METHODS:Data were obtained from the Study of Health in Pomerania (SHIP), a population-based prospectiv...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0031

    authors: Haring R,Völzke H,Felix SB,Schipf S,Dörr M,Rosskopf D,Nauck M,Schöfl C,Wallaschofski H

    更新日期:2009-09-01 00:00:00

  • Skeletal Muscle-Specific Activation of Gq Signaling Maintains Glucose Homeostasis.

    abstract::Skeletal muscle (SKM) insulin resistance plays a central role in the pathogenesis of type 2 diabetes. Because G-protein-coupled receptors (GPCRs) represent excellent drug targets, we hypothesized that activation of specific functional classes of SKM GPCRs might lead to improved glucose homeostasis in type 2 diabetes. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0796

    authors: Bone DBJ,Meister J,Knudsen JR,Dattaroy D,Cohen A,Lee R,Lu H,Metzger D,Jensen TE,Wess J

    更新日期:2019-06-01 00:00:00

  • Inhibition of glucose-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 by epinephrine in pancreatic beta-cells.

    abstract::Glucose sensing is essential for the ability of pancreatic beta-cells to produce insulin in sufficient quantities to maintain blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose by promoting glucose production and inhibiting insulin release. We have...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.04.06.db05-1266

    authors: Gibson TB,Lawrence MC,Gibson CJ,Vanderbilt CA,McGlynn K,Arnette D,Chen W,Collins J,Naziruddin B,Levy MF,Ehrlich BE,Cobb MH

    更新日期:2006-04-01 00:00:00

  • Hyperglycemia suppresses the adrenal medullary response to hypoxemia.

    abstract::An in vivo microdialysis technique was used to study adrenal medullary function in 6 euglycemic and 6 hyperglycemic anesthetized Sprague-Dawley rats exposed to hypoxia. After stabilization of an adrenal dialysis probe, dialyzable adrenal epinephrine and norepinephrine were measured in response to 15 min of 7.8% oxygen...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.5.645

    authors: Cohen WR,Deutsch J

    更新日期:1994-05-01 00:00:00

  • Metabolomics and diabetes: analytical and computational approaches.

    abstract::Diabetes is characterized by altered metabolism of key molecules and regulatory pathways. The phenotypic expression of diabetes and associated complications encompasses complex interactions between genetic, environmental, and tissue-specific factors that require an integrated understanding of perturbations in the netw...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/db14-0509

    authors: Sas KM,Karnovsky A,Michailidis G,Pennathur S

    更新日期:2015-03-01 00:00:00

  • Neonatal rat islet cell cultures synthesize insulin-like growth factor I.

    abstract::Monolayer cultures of islet B-cells were established from neonatal rat pancreas. Serum-free media conditioned by these cultures for 72 h were concentrated and fractionated on Sephadex G-50 at acid pH into a high-molecular-weight pool containing binding protein for insulin-like growth factors (IGFs) and a low-molecular...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.7.696

    authors: Romanus JA,Rabinovitch A,Rechler MM

    更新日期:1985-07-01 00:00:00

  • New approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier.

    abstract::Polyalkylcyanoacrylate nanocapsules (mean size 220 nm), composed of spheric polymeric structures, have been used as a drug carrier for insulin. The rate of encapsulation of insulin is 54.9%, and we studied the therapeutic efficiency of the nanocapsules in diabetic and normal rats. When administered subcutaneously, ins...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.2.246

    authors: Damgé C,Michel C,Aprahamian M,Couvreur P

    更新日期:1988-02-01 00:00:00

  • A novel gene for neonatal diabetes maps to chromosome 10p12.1-p13.

    abstract::We report a genomewide linkage analysis of a large consanguineous family segregating autosomal recessively inherited neonatal diabetes and the identification of a novel neonatal diabetes locus. Neonatal diabetes was characterized by low levels of circulating C-peptide with very low to undetectable levels of insulin in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.10.2636

    authors: Sellick GS,Garrett C,Houlston RS

    更新日期:2003-10-01 00:00:00

  • O-GlcNAcylation of Orphan Nuclear Receptor Estrogen-Related Receptor γ Promotes Hepatic Gluconeogenesis.

    abstract::Estrogen-related receptor γ (ERRγ) is a major positive regulator of hepatic gluconeogenesis. Its transcriptional activity is suppressed by phosphorylation signaled by insulin in the fed state, but whether posttranslational modification alters its gluconeogenic activity in the fasted state is not known. Metabolically a...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1523

    authors: Misra J,Kim DK,Jung YS,Kim HB,Kim YH,Yoo EK,Kim BG,Kim S,Lee IK,Harris RA,Kim JS,Lee CH,Cho JW,Choi HS

    更新日期:2016-10-01 00:00:00

  • Hypoglycemia-associated changes in the electroencephalogram in patients with type 1 diabetes and normal hypoglycemia awareness or unawareness.

    abstract::Hypoglycemia is associated with increased activity in the low-frequency bands in the electroencephalogram (EEG). We investigated whether hypoglycemia awareness and unawareness are associated with different hypoglycemia-associated EEG changes in patients with type 1 diabetes. Twenty-four patients participated in the st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-1359

    authors: Sejling AS,Kjær TW,Pedersen-Bjergaard U,Diemar SS,Frandsen CS,Hilsted L,Faber J,Holst JJ,Tarnow L,Nielsen MN,Remvig LS,Thorsteinsson B,Juhl CB

    更新日期:2015-05-01 00:00:00

  • Influence of polyethylene glycol insulin on lipid tissues of experimental animals.

    abstract::Earlier investigations have revealed that polyethylene glycol-B1-insulin (PEG insulin) causes lower utilization of glucose in fat cells than does the unaltered hormone, even though the blood glucose-lowering activity of both preparations in intact animals is identical. The present study was aimed to establish whether ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.10.953

    authors: Neubauer HP,Obermeier R,Schöne HH

    更新日期:1983-10-01 00:00:00