Abstract:
AIMS/HYPOTHESIS:We previously reported that exposure to antibodies neutralising serpin B13, a protease inhibitor expressed in exocrine pancreatic ducts, promotes beta cell proliferation, underscoring the importance of a functional relationship between exocrine and endocrine pancreas. The aim of the present study was to identify the molecular events that link inhibition of serpin B13 to islet cell proliferation. METHODS:We used an in vitro culture system consisting of isolated pancreatic islets, an extract of pancreatic ductal epithelium and a monoclonal antibody (mAb) to serpin B13 or IgG isotype control. In vivo studies involved treatment of mice with these mAbs. RESULTS:The catalytic activity of cathepsin L (CatL), a cysteine protease target of serpin B13, was augmented in the pancreas of mice injected with serpin B13 mAb. Furthermore, the addition of serpin B13 mAb to the islets, together with the pancreatic ductal epithelium lysate, caused CatL-dependent cleavage of E-cadherin and concomitant upregulation of REG genes, ultimately leading to beta cell proliferation. Direct blockade of E-cadherin with mAb also markedly enhanced REG gene induction, while chemical inhibition of β-catenin, a binding target of E-cadherin, prevented the serpin B13 mAb-induced upregulation of REG genes. CONCLUSIONS/INTERPRETATION:Our work implicates the CatL-E-cadherin-REG pathway in the regulation of islet cell proliferation in response to signals generated in exocrine pancreatic tissue and demonstrates that protease activity may promote adaptive changes in the islets. DATA AVAILABILITY:Microarray data that support the findings of this study have been deposited in Gene Expression Omnibus (GEO) with the accession no. GSE125151.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Lo CW,Kryvalap Y,Sheu TJ,Chang CH,Czyzyk Jdoi
10.1007/s00125-019-4834-0subject
Has Abstractpub_date
2019-05-01 00:00:00pages
822-834issue
5eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-019-4834-0journal_volume
62pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract::Gender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to d...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-019-05040-3
更新日期:2020-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Hyperinsulinaemia and insulin resistance, as well as low IGF-I, have been implicated in the pathogenesis of cardiovascular disease. Little is known about direct effects of IGF-I and insulin on human coronary artery smooth muscle cells (HCASMCs). Our aim was to characterise the expression and function of...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1890-4
更新日期:2005-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Sphingolipid metabolism regulates beta cell biology and inflammation and is abnormal at the onset of type 1 diabetes. Fenofibrate, a regulator of sphingolipid metabolism, is known to prevent diabetes in NOD mice. Here, we aimed to investigate the effects of fenofibrate on the pancreatic lipidome, pancre...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-019-04973-z
更新日期:2019-12-01 00:00:00
abstract::We report the clinical characteristics of all insulin-treated diabetic patients (783 males and 716 females) living on July 1 1973 in a Danish county. In 18 patients diabetes was believed to be secondary to another disease or condition. Of all patients, 43% of the males and 55% of the females were greater than age 50 y...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00279934
更新日期:1983-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. METHODS:A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1792-5
更新日期:2005-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Pancreatic islet transplantation (PIT) offers a physiological treatment for type 1 diabetes, but the failure of islet engraftment hinders its application. The female hormone 17β-oestradiol (E2) favours islet survival and stimulates angiogenesis, raising the possibility that E2 may enhance islet engraftm...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2764-1
更新日期:2013-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Previous studies have implicated the glycoxidative modification of low-density lipoprotein (LDL) by glucose and aldehydes (apparently comprising both glycation and oxidation), as a causative factor in the elevated levels of atherosclerosis observed in diabetic patients. Such LDL modification can result ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1648-4
更新日期:2005-02-01 00:00:00
abstract::Fasting (24 h) normal dogs and depancreatized dogs were injected intravenously with highly purified porcine insulin (Actrapid) in the doses of 0.2 U/kg and 0.5 U/kg, respectively. Blood glucose decreased from 152 +/- 41 (SEM) mg/100 ml to 39 +/- 7 mg/100 ml in the depancreatized dog and from 95 +/- 3 mg/100 ml to 42 +...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF02342872
更新日期:1978-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Recent genome-wide association studies have suggested that a polymorphism in GCKR, the gene encoding the glucokinase regulatory protein, is involved in triacylglycerol regulation. Our aim was to examine in large-scale studies the common GCKR rs780094 polymorphism in relation to metabolic traits (mainly ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0865-z
更新日期:2008-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Despite the overlap in occurrence of cardiovascular disease (CVD) and type 2 diabetes and their risk factors, family history of these diseases has not yet been investigated simultaneously in relation to cardiometabolic markers in offspring. We examined how a family history of CVD and/or diabetes relates...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-016-3988-2
更新日期:2016-08-01 00:00:00
abstract::Under strict balance conditions we studied the effect of phenformin in 5 patients with diabetes mellitus. In all cases phenformin lowered the blood glucose values, and all patients showed a reduction of glycosuria. Contrary to other reports body weight increased during phenformin treatment. This was accompanied by pos...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00429918
更新日期:1975-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs l...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s00125-011-2363-6
更新日期:2012-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:It is difficult to use HbA(1c) as an indicator of glycaemic control in patients with neonatal diabetes mellitus (NDM) because of high levels of fetal haemoglobin (HbF) remaining in the blood. In this study, glycated albumin (GA), which is not affected by HbF, and HbA(1c) were compared to evaluate whethe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2211-8
更新日期:2011-09-01 00:00:00
abstract::Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01223020
更新日期:1978-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to test the hypothesis that intensive glycaemic control (INT) and higher plasma C-peptide levels in patients with poorly controlled diabetes would be associated with better eye outcomes. METHODS:The incidence and progression of diabetic retinopathy (DR) was assessed by grading...
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-014-3199-7
更新日期:2014-06-01 00:00:00
abstract:AIMS:This prospective case-control study aimed at evaluating the time course of serum concentrations of soluble adhesion molecules; intercellular adhesion molecule-1 and L-selectin in siblings with signs of pre-clinical Type 1 diabetes in order to relate these concentrations to autoantibody status and to assess whether...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-003-1072-1
更新日期:2003-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptory (PPARgamma). We hypothesized that the anti-diabetic mechanism of thia...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051218
更新日期:1999-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Currently, three categories of measures are used to assess cardiovascular autonomic dysfunction: measures of the Ewing-test, measures of heart-rate variability, and measures of baroreflex sensitivity. We studied the determinants of these measures obtained from cardiovascular autonomic function tests in ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051344
更新日期:2000-05-01 00:00:00
abstract::Major histocompatibility complex-linked immune response genes are thought to influence susceptibility to induction of both human insulin-dependent diabetes and murine streptozotocin-induced diabetes. To clarify this relationship, we administered streptozotocin intravenously in two doses (120 and 240 mg/kg body weight)...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00275678
更新日期:1984-07-01 00:00:00
abstract::Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050805
更新日期:1997-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Abnormal serum IGF-1 levels are associated with an increased risk of type 2 diabetes and cardiovascular disease. However, the causal role of IGF-1 levels within the normal range in cardiometabolic disease remains unclear. We employed Mendelian randomisation to explore the associations between geneticall...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05190-9
更新日期:2020-09-01 00:00:00
abstract::Mild hypoglycaemia was induced using an artificial pancreas in five normal subjects (from 5.00 +/- 0.15 to 2.83 +/- 0.15 mmol/l) by infusing 28 mU/m2 per min soluble insulin for 60 min. Six Type 1 (insulin-dependent) diabetic patients were stabilized for 14h using an artificial pancreas. They were then rendered hypogl...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00254837
更新日期:1982-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05108-5
更新日期:2020-05-01 00:00:00
abstract::Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, rece...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-015-3844-9
更新日期:2016-03-01 00:00:00
abstract::Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00869268
更新日期:1986-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:The cyclooxygenase-2 (PTGS2, previously known as COX2) enzyme and its products, such as prostaglandin E(2) (PGE(2)), have been implicated in the pathogenesis of several inflammatory diseases including islet dysfunction under diabetic conditions. In this study we evaluated whether diabetic conditions in ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-0065-7
更新日期:2006-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Microvascular endothelial hyperpermeability, mainly caused by claudin-5 deficiency, is the initial pathological change that occurs in diabetes-associated cardiovascular disease. The ketone body β-hydroxybutyrate (BHB) exerts unique beneficial effects on the cardiovascular system, but the involvement of ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05305-2
更新日期:2021-01-01 00:00:00
abstract::Loss of neurogenic inflammation in response to tissue injury may be an important complication of diabetes mellitus. We studied local neurogenic inflammation in the peripheral nerve trunk of Sprague-Dawley rats 4 months following the induction of diabetes by streptozotocin injection. To assess neurogenic inflammation, ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF02743263
更新日期:1993-06-01 00:00:00
abstract::Glycerol release from epididymal fat fragments of young adult (3-month old) ob/ob mice was three times lower than normal, on a tissue weight basis. Dose-response curves in response to isoproterenol and ACTH-(1--24) indicated that the capacity of the lipolytic process was reduced. However, the sensitivity to both hormo...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01236307
更新日期:1977-12-01 00:00:00
abstract::We have investigated whether and how the elevated glucose concentrations characteristic of diabetes may alter the interaction of endothelial cells with low-density lipoproteins (LDL). Protracted exposure of cultured human endothelial cells to 20 mmol/l glucose failed to affect either the relationship between the degre...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00252411
更新日期:1984-03-01 00:00:00