Human prohormone convertase 3 gene: exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM.

Abstract:

:Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3). PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide. Thus, PC3 plays a key role in regulating insulin biosynthesis. Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing. NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder. To examine this hypothesis, we have isolated and characterized the human PC3 gene and screened it for mutations in a group of Japanese subjects with NIDDM. The PC3 gene consists of 14 exons spanning more than 35 kb. The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family. Single-strand conformational analysis and nucleotide sequencing of the entire coding region of the PC3 gene in 102 Japanese subjects with NIDDM revealed missense mutations in exons 2 (Arg/Gln53) and 14 (Gln/Glu638), neither of which was associated with NIDDM in this population. These data suggest that genetic variation in the PC3 gene is unlikely to be a major contributor to NIDDM susceptibility in Japanese.

journal_name

Diabetes

journal_title

Diabetes

authors

Ohagi S,Sakaguchi H,Sanke T,Tatsuta H,Hanabusa T,Nanjo K

doi

10.2337/diab.45.7.897

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

897-901

issue

7

eissn

0012-1797

issn

1939-327X

journal_volume

45

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors.

    abstract::The ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of islet allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. However, transient transgene expression and the tendency...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.3.515

    authors: Flotte T,Agarwal A,Wang J,Song S,Fenjves ES,Inverardi L,Chesnut K,Afione S,Loiler S,Wasserfall C,Kapturczak M,Ellis T,Nick H,Atkinson M

    更新日期:2001-03-01 00:00:00

  • Atrasentan Reduces Albuminuria by Restoring the Glomerular Endothelial Glycocalyx Barrier in Diabetic Nephropathy.

    abstract::Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial g...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1413

    authors: Boels MG,Avramut MC,Koudijs A,Dane MJ,Lee DH,van der Vlag J,Koster AJ,van Zonneveld AJ,van Faassen E,Gröne HJ,van den Berg BM,Rabelink TJ

    更新日期:2016-08-01 00:00:00

  • Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

    abstract::Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 mont...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db16-0823

    authors: Haller MJ,Gitelman SE,Gottlieb PA,Michels AW,Perry DJ,Schultz AR,Hulme MA,Shuster JJ,Zou B,Wasserfall CH,Posgai AL,Mathews CE,Brusko TM,Atkinson MA,Schatz DA

    更新日期:2016-12-01 00:00:00

  • Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.

    abstract:OBJECTIVE:Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary hu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0583

    authors: Bouzakri K,Austin R,Rune A,Lassman ME,Garcia-Roves PM,Berger JP,Krook A,Chibalin AV,Zhang BB,Zierath JR

    更新日期:2008-06-01 00:00:00

  • Modulation of growth hormone signal transduction in kidneys of streptozotocin-induced diabetic animals: effect of a growth hormone receptor antagonist.

    abstract::Growth hormone (GH) and IGFs have a long distinguished history in diabetes, with possible participation in the development of renal complications. The implicated effect of GH in diabetic end-stage organ damage may be mediated by growth hormone receptor (GHR) or postreceptor events in GH signal transduction. The presen...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.7.2270

    authors: Thirone AC,Scarlett JA,Gasparetti AL,Araujo EP,Lima MH,Carvalho CR,Velloso LA,Saad MJ

    更新日期:2002-07-01 00:00:00

  • Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change.

    abstract::Because it is unknown whether 24-h energy expenditure (EE) responses to dietary extremes will identify phenotypes associated with weight regulation, the aim of this study was to determine whether such responses to fasting or overfeeding are associated with future weight change. The 24-h EE during energy balance, fasti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0382

    authors: Schlögl M,Piaggi P,Pannacciuli N,Bonfiglio SM,Krakoff J,Thearle MS

    更新日期:2015-11-01 00:00:00

  • Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.

    abstract:OBJECTIVE:White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0929

    authors: Cheng Y,Meng Q,Wang C,Li H,Huang Z,Chen S,Xiao F,Guo F

    更新日期:2010-01-01 00:00:00

  • Protection Against Insulin Resistance by Apolipoprotein M/Sphingosine-1-Phosphate.

    abstract::Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL ar...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0811

    authors: Kurano M,Tsukamoto K,Shimizu T,Kassai H,Nakao K,Aiba A,Hara M,Yatomi Y

    更新日期:2020-05-01 00:00:00

  • Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice.

    abstract::Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.2.376

    authors: Masaki T,Yoshimatsu H,Chiba S,Watanabe T,Sakata T

    更新日期:2001-02-01 00:00:00

  • Structure, function, and immunogenicity of human insulinoma cells.

    abstract::Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.9.1279

    authors: Thivolet CH,Demidem A,Haftek M,Durand A,Bertrand J

    更新日期:1988-09-01 00:00:00

  • Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults.

    abstract::Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 ob...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db15-0675

    authors: Johnson ML,Distelmaier K,Lanza IR,Irving BA,Robinson MM,Konopka AR,Shulman GI,Nair KS

    更新日期:2016-01-01 00:00:00

  • C-peptide activates AMPKα and prevents ROS-mediated mitochondrial fission and endothelial apoptosis in diabetes.

    abstract::Vasculopathy is a major complication of diabetes; however, molecular mechanisms mediating the development of vasculopathy and potential strategies for prevention have not been identified. We have previously reported that C-peptide prevents diabetic vasculopathy by inhibiting reactive oxygen species (ROS)-mediated endo...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0039

    authors: Bhatt MP,Lim YC,Kim YM,Ha KS

    更新日期:2013-11-01 00:00:00

  • TBC1D4 Is Necessary for Enhancing Muscle Insulin Sensitivity in Response to AICAR and Contraction.

    abstract::Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. We recently demonstrated that AMPK is necessary for AICAR, contraction, and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent ske...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0769

    authors: Kjøbsted R,Chadt A,Jørgensen NO,Kido K,Larsen JK,de Wendt C,Al-Hasani H,Wojtaszewski JFP

    更新日期:2019-09-01 00:00:00

  • Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo.

    abstract:OBJECTIVE:Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose tr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0120

    authors: Chari M,Yang CS,Lam CK,Lee K,Mighiu P,Kokorovic A,Cheung GW,Lai TY,Wang PY,Lam TK

    更新日期:2011-07-01 00:00:00

  • Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility.

    abstract::Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistan...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.3.688

    authors: Lan H,Rabaglia ME,Stoehr JP,Nadler ST,Schueler KL,Zou F,Yandell BS,Attie AD

    更新日期:2003-03-01 00:00:00

  • Altered hepatic and muscle substrate utilization provoked by GLUT4 ablation.

    abstract::Studies were conducted to explore altered substrate utilization and metabolism in GLUT4 null mice. Liver fatty acid synthase mRNA and fatty acid synthesis rates were dramatically increased in GLUT4 null mice compared with control mice and were supported by increased rates of the pentose phosphate pathway oxidative pha...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.4.935

    authors: Ranalletta M,Jiang H,Li J,Tsao TS,Stenbit AE,Yokoyama M,Katz EB,Charron MJ

    更新日期:2005-04-01 00:00:00

  • Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.

    abstract::To define the mechanisms involved in the evolution of diabetes in the Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by immunochemistry, point-counting morphometry, and 6-h 5-bromo-2'-deoxyuridine (BrdU) incorporation. The beta-cell mass in 5- to 7-week-old prediabetic ZDF rats (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.3.358

    authors: Pick A,Clark J,Kubstrup C,Levisetti M,Pugh W,Bonner-Weir S,Polonsky KS

    更新日期:1998-03-01 00:00:00

  • Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin.

    abstract:OBJECTIVE:Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extra...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0822

    authors: Rahmouni K,Sigmund CD,Haynes WG,Mark AL

    更新日期:2009-03-01 00:00:00

  • Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides.

    abstract::The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.3.301

    authors: Gordon EE,Duga J

    更新日期:1975-03-01 00:00:00

  • Emerging Role of Bone Morphogenetic Protein 4 in Metabolic Disorders.

    abstract::Bone morphogenetic proteins (BMPs) are a group of signaling molecules that belong to the TGF-β superfamily. Initially discovered for their ability to induce bone formation, BMPs are known to play a diverse and critical array of biological roles. We here focus on recent evidence showing that BMP4 is an important regula...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db20-0884

    authors: Baboota RK,Blüher M,Smith U

    更新日期:2021-02-01 00:00:00

  • Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus.

    abstract::The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus. To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.4.828

    authors: Baskin DG,Breininger JF,Schwartz MW

    更新日期:1999-04-01 00:00:00

  • 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)...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.50.2007.s154

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

    更新日期:2001-02-01 00:00:00

  • Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.

    abstract::Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involve...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.2.227

    authors: Shintani M,Ogawa Y,Ebihara K,Aizawa-Abe M,Miyanaga F,Takaya K,Hayashi T,Inoue G,Hosoda K,Kojima M,Kangawa K,Nakao K

    更新日期:2001-02-01 00:00:00

  • Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in beta-cells.

    abstract::Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here,...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.1.228

    authors: Mulder H,Holst LS,Svensson H,Degerman E,Sundler F,Ahrén B,Rorsman P,Holm C

    更新日期:1999-01-01 00:00:00

  • Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes.

    abstract::Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1459

    authors: Nilsson E,Jansson PA,Perfilyev A,Volkov P,Pedersen M,Svensson MK,Poulsen P,Ribel-Madsen R,Pedersen NL,Almgren P,Fadista J,Rönn T,Klarlund Pedersen B,Scheele C,Vaag A,Ling C

    更新日期:2014-09-01 00:00:00

  • Failure of genetically selected miniature swine to model NIDDM.

    abstract::Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.3.284

    authors: Hand MS,Surwit RS,Rodin J,Van Order P,Feinglos MN

    更新日期:1987-03-01 00:00:00

  • Effect of physical exercise on secretion of growth hormone, glucagon, and cortisol in obese and diabetic children.

    abstract::The effect of muscular exertion of moderate intensity on blood sugar (BS), plasma levels of growth hormone (GH), glucagon, and cortisol (F) has been studied in endocrinologically normal children with short stature and compared with children with clinical diabetes mellitus and obese children with normal and diminished ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.8.758

    authors: Garlaschi C,di Natale B,del Guercio MJ,Caccamo A,Gargantini L,Chiumello G

    更新日期:1975-08-01 00:00:00

  • Relationship between diurnal blood pressure, renal hemodynamic function, and the renin-angiotensin system in type 1 diabetes.

    abstract::In patients with diabetes, altered diurnal blood pressure (BP) regulation (high night-to-day [N/D] ratio, or "nondipping") is associated with increases in albumin excretion and a decline in the glomerular filtration rate (GFR) by an unknown mechanism. Because it is known that renin angiotensin system (RAS) activation ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.7.1806

    authors: Miller JA,Curtis JR,Sochett EB

    更新日期:2003-07-01 00:00:00

  • Muscle glycogen synthesis and disposition of infused glucose in humans with reduced rates of insulin-mediated carbohydrate storage.

    abstract::Six men with a low rate of insulin-stimulated, non-oxidative carbohydrate disposal (storage) and six with a high storage rate were recruited for study of the fate of insulin-stimulated glucose uptake. [3-3H]glucose was infused before and during a 4-h hyperinsulinemic euglycemic clamp procedure in a dosage regimen desi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.3.303

    authors: Young AA,Bogardus C,Wolfe-Lopez D,Mott DM

    更新日期:1988-03-01 00:00:00

  • The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells.

    abstract::Defects in insulin secretion, resulting from loss of function or destruction of pancreatic beta-cells, trigger diabetes. Interleukin (IL)-1beta is a proinflammatory cytokine that is involved in type 1 and type 2 diabetes development and impairs beta-cell survival and function. Because effective insulin signaling is re...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.suppl_3.s97

    authors: Emanuelli B,Glondu M,Filloux C,Peraldi P,Van Obberghen E

    更新日期:2004-12-01 00:00:00