A Primary Role for α-Cells as Amino Acid Sensors.

Abstract:

:Glucagon and its partner insulin are dually linked in both their secretion from islet cells and their action in the liver. Glucagon signaling increases hepatic glucose output, and hyperglucagonemia is partly responsible for the hyperglycemia in diabetes, making glucagon an attractive target for therapeutic intervention. Interrupting glucagon signaling lowers blood glucose but also results in hyperglucagonemia and α-cell hyperplasia. Investigation of the mechanism for α-cell proliferation led to the description of a conserved liver-α-cell axis where glucagon is a critical regulator of amino acid homeostasis. In return, amino acids regulate α-cell function and proliferation. New evidence suggests that dysfunction of the axis in humans may result in the hyperglucagonemia observed in diabetes. This discussion outlines important but often overlooked roles for glucagon that extend beyond glycemia and supports a new role for α-cells as amino acid sensors.

journal_name

Diabetes

journal_title

Diabetes

authors

Dean ED

doi

10.2337/dbi19-0021

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

542-549

issue

4

eissn

0012-1797

issn

1939-327X

pii

dbi19-0021

journal_volume

69

pub_type

杂志文章,评审

相关文献

DIABETES文献大全
  • Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets.

    abstract:OBJECTIVE:Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, re...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0724

    authors: Olerud J,Johansson M,Lawler J,Welsh N,Carlsson PO

    更新日期:2008-07-01 00:00:00

  • Heparanase is essential for the development of diabetic nephropathy in mice.

    abstract::Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permselectivity of glomerular basement membrane (GBM) plays an important role in DN pathogenesis. Heparanase is the predominant enzyme that degrades heparan sulfate (HS), the main polysaccharide of the GBM. Loss of GBM HS in dia...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1024

    authors: Gil N,Goldberg R,Neuman T,Garsen M,Zcharia E,Rubinstein AM,van Kuppevelt T,Meirovitz A,Pisano C,Li JP,van der Vlag J,Vlodavsky I,Elkin M

    更新日期:2012-01-01 00:00:00

  • Newly identified pancreatic protein islet amyloid polypeptide. What is its relationship to diabetes?

    abstract::Islet amyloid polypeptide (IAPP) or amylin is a newly identified 37-amino acid COOH-terminal-amidated polypeptide that is the major protein constituent of amyloid deposits in insulinomas and amyloid deposits in pancreatic islets of non-insulin-dependent (type II) diabetic humans and adult diabetic cats. IAPP is stored...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.40.3.310

    authors: Johnson KH,O'Brien TD,Westermark P

    更新日期:1991-03-01 00:00:00

  • Increased glucose sensitivity of stimulus-secretion coupling in islets from Psammomys obesus after diet induction of diabetes.

    abstract::When fed a high-energy (HE) diet, diabetes-prone (DP) Psammomys obesus develop type 2 diabetes with altered glucose-stimulated insulin secretion (GSIS). Beta-cell stimulus-secretion coupling was investigated in islets isolated from DP P. obesus fed a low-energy (LE) diet (DP-LE) and after 5 days on a HE diet (DP-HE). ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.8.2552

    authors: Pertusa JA,Nesher R,Kaiser N,Cerasi E,Henquin JC,Jonas JC

    更新日期:2002-08-01 00:00:00

  • Multiple redox forms of the insulin receptor in native liver membranes.

    abstract::Three forms of disulfide-linked insulin receptor complexes are labeled by covalent cross-linking to receptor-bound 125I-insulin in native adipocyte or liver membranes. These receptors of Mr 350,000 Mr 320,000, and Mr 290,000 are composed of alpha (Mr 125,000), beta(Mr 90,000), and beta 1(Mr 49,000) subunits in stoichi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.11.945

    authors: Massaqué J,Czech MP

    更新日期:1980-11-01 00:00:00

  • Perfect normalization of excessive glucagon responses to intravenous arginine in human diabetes mellitus with the artificial beta-cell.

    abstract::To elucidate the precise significance of pancreatic A-cell hypersecretion in the pathogenesis of diabetes mellitus, the change in the immunoreactive glucagon (IRG) response to intravenous arginine was studied in both nonobese, hypoinsulinemic non-insulin-dependent (NIDDM) and insulin-dependent diabetic (IDDM) subjects...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.9.762

    authors: Kawamori R,Shichiri M,Kikuchi M,Yamasaki Y,Abe H

    更新日期:1980-09-01 00:00:00

  • Effects of differing antecedent increases of plasma cortisol on counterregulatory responses during subsequent exercise in type 1 diabetes.

    abstract:OBJECTIVE:Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next-day exercise in type 1 diabetes. The aim of this study was to determine whether antecedent increase of plasma cortisol is a mechanism responsible for this finding. RESEARCH DESIGN AND METHODS:For this study, 22 ty...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db09-0382

    authors: Bao S,Briscoe VJ,Tate DB,Davis SN

    更新日期:2009-09-01 00:00:00

  • Marked increase in white adipose tissue blood perfusion in the type 2 diabetic GK rat.

    abstract::The aim of the present study was to evaluate and cor-relate islet to brown and white adipose tissue (WAT) blood perfusion in one obese rat and one nonobese rat with type 2 diabetes (obese Zucker [OZ] and GK rats, respectively). We measured blood perfusion with a microsphere technique in anesthetized animals and subseq...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.9.2620

    authors: Kampf C,Bodin B,Källskog O,Carlsson C,Jansson L

    更新日期:2005-09-01 00:00:00

  • Mechanisms to Elevate Endogenous GLP-1 Beyond Injectable GLP-1 Analogs and Metabolic Surgery.

    abstract::Therapeutic engineering of glucagon-like peptide 1 (GLP-1) has enabled development of new medicines to treat type 2 diabetes. These injectable analogs achieve robust glycemic control by increasing concentrations of "GLP-1 equivalents" (∼50 pmol/L). Similar levels of endogenous GLP-1 occur after gastric bypass surgery,...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-0607

    authors: Briere DA,Bueno AB,Gunn EJ,Michael MD,Sloop KW

    更新日期:2018-02-01 00:00:00

  • Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach.

    abstract::Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese ty...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.5.1054

    authors: Nagasaka S,Tokuyama K,Kusaka I,Hayashi H,Rokkaku K,Nakamura T,Kawakami A,Higashiyama M,Ishikawa S,Saito T

    更新日期:1999-05-01 00:00:00

  • Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.

    abstract::Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). W...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db10-0902

    authors: Gögebakan Ö,Andres J,Biedasek K,Mai K,Kühnen P,Krude H,Isken F,Rudovich N,Osterhoff MA,Kintscher U,Nauck M,Pfeiffer AF,Spranger J

    更新日期:2012-02-01 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

  • Hyperlipoproteinemia in streptozotocin-treated rats.

    abstract::In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.6.509

    authors: Bar-On H,Roheim PS,Eder HA

    更新日期:1976-06-01 00:00:00

  • Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a patient with severe early-onset obesity is due to a dominant-negative effect caused by receptor dimerization.

    abstract::Mutations in the melanocortin-4 receptor (MC4R) gene are the most frequent monogenic causes of severe obesity. Most mutations have been described as heterozygous with loss of function, suggesting that haploinsufficiency is the most likely mechanism of dominant inheritance. We detected a heterozygous mutation, D90N, in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.12.2984

    authors: Biebermann H,Krude H,Elsner A,Chubanov V,Gudermann T,Grüters A

    更新日期:2003-12-01 00:00:00

  • Acute bidirectional manipulation of muscle glucose uptake by in vivo electrotransfer of constructs targeting glucose transporter genes.

    abstract::Analysis of conventional germ-line or tissue-specific gene manipulation in vivo is potentially confounded by developmental adaptation of animal physiology. We aimed to adapt the technique of in vivo electrotransfer (IVE) to alter local gene expression in skeletal muscle of rodents as a means of investigating the role ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.9.2702

    authors: Cleasby ME,Davey JR,Reinten TA,Graham MW,James DE,Kraegen EW,Cooney GJ

    更新日期:2005-09-01 00:00:00

  • Increased expression of Gi-coupled muscarinic acetylcholine receptor and Gi in atrium of elderly diabetic subjects.

    abstract::In an ongoing investigation of the effects of age on G protein-coupled receptor signaling in human atrial tissue, we have found that the density of atrial muscarinic acetylcholine receptor (mAChR) increases with age but reaches statistical significance only in patients with diabetes. Moreover, we find that in elderly ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.9.2392

    authors: Richardson MD,Kilts JD,Kwatra MM

    更新日期:2004-09-01 00:00:00

  • Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.

    abstract::Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-0578

    authors: Yoshimatsu G,Kunnathodi F,Saravanan PB,Shahbazov R,Chang C,Darden CM,Zurawski S,Boyuk G,Kanak MA,Levy MF,Naziruddin B,Lawrence MC

    更新日期:2017-11-01 00:00:00

  • Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1).

    abstract::C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin be...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.02.06.db05-0733

    authors: Schmidt G,Sirois F,Anini Y,Kauri LM,Gyamera-Acheampong C,Fleck E,Scott FW,Chrétien M,Mbikay M

    更新日期:2006-02-01 00:00:00

  • Pulsatile insulin secretion from isolated human pancreatic islets.

    abstract::Insulin secretion from the pancreas is pulsatile. The precise site and function of the pacemaker that regulates insulin periodicity in humans have not been determined. We isolated human pancreatic islets from five cadaver organ donors by collagenase digestion and density gradient purification. After 24 h of culture in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.6.827

    authors: Marchetti P,Scharp DW,Mclear M,Gingerich R,Finke E,Olack B,Swanson C,Giannarelli R,Navalesi R,Lacy PE

    更新日期:1994-06-01 00:00:00

  • Ghrelin attenuates the inhibitory effects of glucagon-like peptide-1 and peptide YY(3-36) on food intake and gastric emptying in rats.

    abstract::Ghrelin stimulates, while glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) [PYY(3-36)] inhibit, food intake and gastric emptying in rats. We determined the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake in freely feeding rats, and on the inhibitory effects of intraveno...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0730

    authors: Chelikani PK,Haver AC,Reidelberger RD

    更新日期:2006-11-01 00:00:00

  • A novel role for CD36 in VLDL-enhanced platelet activation.

    abstract::Type 2 diabetes is characterized by increased plasma triglyceride levels and a fourfold increase in ischemic heart disease, but the mechanism is unclear. CD36 is a receptor/transporter that binds fatty acids of lipoproteins. CD36 deficiency has been linked with insulin resistance. There is strong evidence of in vivo i...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.5.1248

    authors: Englyst NA,Taube JM,Aitman TJ,Baglin TP,Byrne CD

    更新日期:2003-05-01 00:00:00

  • Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

    abstract::The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein respon...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.46.12.2082

    authors: Dullaart RP,Hoogenberg K,Riemens SC,Groener JE,van Tol A,Sluiter WJ,Stulp BK

    更新日期:1997-12-01 00:00:00

  • Genetics of NIDDM in France: studies with 19 candidate genes in affected sib pairs.

    abstract::As part of an ongoing search for susceptibility loci for NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action for linkage with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regul...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.6.1062

    authors: Vionnet N,Hani EH,Lesage S,Philippi A,Hager J,Varret M,Stoffel M,Tanizawa Y,Chiu KC,Glaser B,Permutt MA,Passa P,Demenais F,Froguel P

    更新日期:1997-06-01 00:00:00

  • Rapid increase in circulating leptin in ventromedial hypothalamus-lesioned rats: role of hyperinsulinemia and implication for upregulation mechanism.

    abstract::The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels co...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.10.2034

    authors: Suga A,Hirano T,Kageyama H,Kashiba M,Oka J,Osaka T,Namba Y,Tsuji M,Miura M,Adachi M,Inoue S

    更新日期:1999-10-01 00:00:00

  • Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients.

    abstract::Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE recept...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.5.1214

    authors: Poirier O,Nicaud V,Vionnet N,Raoux S,Tarnow L,Vlassara H,Parving HH,Cambien F

    更新日期:2001-05-01 00:00:00

  • Adrenergic mediation of hypoglycemia-associated autonomic failure.

    abstract:OBJECTIVE:We tested the hypothesis that adrenergic activation, cholinergic activation, or both, mediate the effect of recent antecedent hypoglycemia to reduce the sympathoadrenal response to subsequent hypoglycemia, the key feature of hypoglycemia-associated autonomic failure in diabetes, in humans. RESEARCH DESIGN AN...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-1374

    authors: Ramanathan R,Cryer PE

    更新日期:2011-02-01 00:00:00

  • T-Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal.

    abstract::The autoimmune disease type 1 diabetes is characterized by effector T-cell responses to pancreatic β-cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to β-cell demise and insulin insufficiency. Although a given HLA molecule presents a vast array of peptides, only those recogniz...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/dbi19-0022

    authors: James EA,Mallone R,Kent SC,DiLorenzo TP

    更新日期:2020-07-01 00:00:00

  • Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.

    abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0122

    authors: Berglund LM,Lyssenko V,Ladenvall C,Kotova O,Edsfeldt A,Pilgaard K,Alkayyali S,Brøns C,Forsblom C,Jonsson A,Zetterqvist AV,Nitulescu M,McDavitt CR,Dunér P,Stancáková A,Kuusisto J,Ahlqvist E,Lajer M,Tarnow L,Madsbad S

    更新日期:2016-01-01 00:00:00

  • Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells.

    abstract::Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. We examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.11.2720

    authors: Zhang B,Hosaka M,Sawada Y,Torii S,Mizutani S,Ogata M,Izumi T,Takeuchi T

    更新日期:2003-11-01 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