ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion.

Abstract:

:Closure of ATP-regulated K(+) channels (K(ATP) channels) plays a central role in glucose-stimulated insulin secretion in beta cells. K(ATP) channels are also highly expressed in glucagon-producing alpha cells, where their function remains unresolved. Under hypoglycaemic conditions, K(ATP) channels are open in alpha cells but their activity is low and only ~1% of that in beta cells. Like beta cells, alpha cells respond to hyperglycaemia with K(ATP) channel closure, membrane depolarisation and stimulation of action potential firing. Yet, hyperglycaemia reciprocally regulates glucagon (inhibition) and insulin secretion (stimulation). Here we discuss how this conundrum can be resolved and how reduced K(ATP) channel activity, via membrane depolarisation, paradoxically reduces alpha cell Ca(2+) entry and glucagon exocytosis. Finally, we consider whether the glucagon secretory defects associated with diabetes can be attributed to impaired K(ATP) channel regulation and discuss the potential for remedial pharmacological intervention using sulfonylureas.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Rorsman P,Ramracheya R,Rorsman NJ,Zhang Q

doi

10.1007/s00125-014-3279-8

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

1749-61

issue

9

eissn

0012-186X

issn

1432-0428

journal_volume

57

pub_type

杂志文章,评审
  • Effect of metergoline, a powerful and long-acting antiserotoninergic agent, on insulin secretion in normal subjects and in patients with chemical diabetes.

    abstract::The effect of metergoline on insulin secretion has been evaluated in normal subjects and in patients with chemical diabetes. The repeated administration of metergoline, 2 mg at four-hour intervals to give a total of 24 mg, has enhanced insulin secretion in response to i.v. glucose in normal subjects but not in chemica...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00429842

    authors: Pontiroli AE,Viberti GC,Tognetti A,Pozza G

    更新日期:1975-04-01 00:00:00

  • Subclinical nerve dysfunction in children and adolescents with IDDM.

    abstract::The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00401840

    authors: Hyllienmark L,Brismar T,Ludvigsson J

    更新日期:1995-06-01 00:00:00

  • Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study.

    abstract::The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 Eu...

    journal_title:Diabetologia

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s001250050736

    authors: Greaves M,Malia RG,Goodfellow K,Mattock M,Stevens LK,Stephenson JM,Fuller JH

    更新日期:1997-06-01 00:00:00

  • Mutation at position -132 in the islet amyloid polypeptide ( IAPP) gene promoter enhances basal transcriptional activity through a new CRE-like binding site.

    abstract:AIMS/HYPOTHESIS:Mutations in the islet amyloid polypeptide ( IAPP) gene may play a potential role in the abnormal regulation or expression of the peptide. The aim of this study was to determine the functional role of the -132 G/A mutation reported in the promoter region of the IAPP gene in a population of Spanish Type ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-004-1439-y

    authors: Novials A,Mato E,Lucas M,Franco C,Rivas M,Santisteban P,Gomis R

    更新日期:2004-07-01 00:00:00

  • Glucocorticoids and the fate of exogenous insulin in insulin-immunized guinea pigs.

    abstract::Groups of normal rats and of normal and insulin-immunized guinea pigs were injected intravasculary with mixtures of radio-iodinated and unlabelled porcine insulins. No differences could be discerned between the fates of radio-iodinated and unlabelled insulins in normal or immune guinea pigs except with respect to the ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00422391

    authors: Wright PH,Gingerich RL,Oliver JR

    更新日期:1975-08-01 00:00:00

  • Diurnal rhythm in endogenous glucose production is a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour?

    abstract:AIMS/HYPOTHESIS:An increase in endogenous glucose production (EGP) is a major contributor to fasting morning hyperglycaemia in type 2 diabetes. This increase is dissipated with fasting, later in the day. To understand its origin, EGP, gluconeogenesis and hormones that regulate metabolism were measured over 24 h. We hyp...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-006-0273-9

    authors: Radziuk J,Pye S

    更新日期:2006-07-01 00:00:00

  • Secular trend for mortality from breast cancer and the association between diabetes and breast cancer in Taiwan between 1995 and 2006.

    abstract:AIMS/HYPOTHESIS:Studies have identified an association between diabetes and breast cancer in postmenopausal women in Western countries. Such an association needs to be confirmed in an Asian population. The aim of this study was to evaluate the secular trend for breast cancer mortality in Taiwanese women in the general ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-1204-8

    authors: Tseng CH,Chong CK,Tai TY

    更新日期:2009-02-01 00:00:00

  • The postprandial state does not impair endothelial function in women with type 2 diabetes irrespective of glycaemic control.

    abstract:AIMS/HYPOTHESIS:The postprandial state has been shown to be associated with endothelial dysfunction, a predictor of cardiovascular morbidity. In type 2 diabetes, postprandial metabolic excursions are prolonged and exaggerated, but less pronounced if glycaemic control is optimised. We investigated the impact of improved...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-004-1534-0

    authors: Strey CH,Young J,Collier M,Florkowski CM,Shand BI,Scott RS

    更新日期:2004-10-01 00:00:00

  • Pancreas transplantation: assessing secondary complications and life quality.

    abstract::Two sequential studies of life quality among pancreas transplant recipients are reported. The first study (n = 32) investigated symptoms of neuropathy, enteropathy and retinopathy, along with well-being post successful transplantation. Patients noted improvement in secondary complications, were satisfied with the proc...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00587641

    authors: Zehr PS,Milde FK,Hart LK,Corry RJ

    更新日期:1991-08-01 00:00:00

  • Markers of insulin resistance are associated with fatness and fitness in school-aged children: the European Youth Heart Study.

    abstract:AIMS/HYPOTHESIS:Our aim was to examine the association between markers of insulin resistance and: (1) body fat and waist circumference, taking into account cardiorespiratory fitness in school-aged children; and (2) cardiorespiratory fitness at differing levels of body fat and waist circumference. SUBJECTS AND METHODS:...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-007-0678-0

    authors: Ruiz JR,Rizzo NS,Ortega FB,Loit HM,Veidebaum T,Sjöström M

    更新日期:2007-07-01 00:00:00

  • Type 2 (non-insulin-dependent) diabetes mellitus, migration and westernisation: the Tokelau Island Migrant Study.

    abstract::The migration of Tokelauans from a traditional atoll in the Pacific to urban New Zealand is associated with an increased prevalence and incidence of Type 2 (non-insulin-dependent) diabetes mellitus over the period 1968-1982. During the same period, a lesser but definite increase is seen among non-migrants in Tokelau. ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00285332

    authors: Ostbye T,Welby TJ,Prior IA,Salmond CE,Stokes YM

    更新日期:1989-08-01 00:00:00

  • Analysis of the HepG2/erythrocyte glucose transporter locus in a family with type 2 (non-insulin-dependent) diabetes and obesity.

    abstract::A recent report has shown an association between a specific Xba1 restriction fragment of the human HepG2-Erythrocyte glucose transporter gene and Type 2 (non-insulin dependent) diabetes. To further examine the significance of this finding we have studied Type 2 diabetic pedigrees for linkage between the Xba1 alleles o...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00285296

    authors: O'Rahilly S,Patel P,Wainscoat JS,Turner RC

    更新日期:1989-04-01 00:00:00

  • Correction to: Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis.

    abstract::AbstractIn Table 1 the data for age group, sex and Townsend index were incorrectly identified as mean ± SD instead of n (%). The table is corrected here. ...

    journal_title:Diabetologia

    pub_type: 杂志文章,已发布勘误

    doi:10.1007/s00125-018-4620-4

    authors: Nirantharakumar K,Mohammed N,Toulis KA,Thomas GN,Narendran P

    更新日期:2018-07-01 00:00:00

  • The promise of stem cell-derived islet replacement therapy.

    abstract::Present-day treatments for people that are insulin dependent require multiple insulin injections, sometimes with an insulin pump, coupled with regular blood glucose monitoring. The availability of modified insulins, each with peaks of activity at varying times, has improved diabetes management. On the other hand, ther...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-020-05367-2

    authors: Melton D

    更新日期:2021-01-16 00:00:00

  • Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile.

    abstract::Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tro...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00282238

    authors: Mohan V,Mohan R,Susheela L,Snehalatha C,Bharani G,Mahajan VK,Ramachandran A,Viswanathan M,Kohner EM

    更新日期:1985-04-01 00:00:00

  • Sex differences in metabolic regulation and diabetes susceptibility.

    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

    authors: Tramunt B,Smati S,Grandgeorge N,Lenfant F,Arnal JF,Montagner A,Gourdy P

    更新日期:2020-03-01 00:00:00

  • Immunological heterogeneity in type I diabetes: presence of distinct autoantibody patterns in patients with acute onset and slowly progressive disease.

    abstract::Type I diabetes mellitus may represent a heterogeneous disorder with a distinct pathogenesis in patients with young and adult onset of the disease. To investigate whether serological markers directed to different autoantigens have the potential to distinguish acute onset from slowly progressive Type I diabetes we anal...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250051004

    authors: Seissler J,de Sonnaville JJ,Morgenthaler NG,Steinbrenner H,Glawe D,Khoo-Morgenthaler UY,Lan MS,Notkins AL,Heine RJ,Scherbaum WA

    更新日期:1998-08-01 00:00:00

  • B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

    abstract:AIMS/HYPOTHESIS:B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. ...

    journal_title:Diabetologia

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00125-011-2392-1

    authors: Heinisch BB,Vila G,Resl M,Riedl M,Dieplinger B,Mueller T,Luger A,Pacini G,Clodi M

    更新日期:2012-05-01 00:00:00

  • Receptor for AGEs (RAGE) blockade may exert its renoprotective effects in patients with diabetic nephropathy via induction of the angiotensin II type 2 (AT2) receptor.

    abstract:AIMS/HYPOTHESIS:The receptor for AGEs (RAGE) contributes to the development and progression of diabetic nephropathy. In this study, we examined whether the protective effects of RAGE blockade are exerted via modulation of the renal angiotensin II type 2 (AT2) receptor. METHODS:Control and streptozotocin diabetic mice,...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-010-1837-2

    authors: Sourris KC,Morley AL,Koitka A,Samuel P,Coughlan MT,Penfold SA,Thomas MC,Bierhaus A,Nawroth PP,Yamamoto H,Allen TJ,Walther T,Hussain T,Cooper ME,Forbes JM

    更新日期:2010-11-01 00:00:00

  • Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young.

    abstract:AIMS/HYPOTHESIS:Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as 'maturity-onset diabetes of the young'. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive i...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-0942-y

    authors: Ellard S,Bellanné-Chantelot C,Hattersley AT,European Molecular Genetics Quality Network (EMQN) MODY group.

    更新日期:2008-04-01 00:00:00

  • Burden of diabetes in Australia: life expectancy and disability-free life expectancy in adults with diabetes.

    abstract:AIMS/HYPOTHESIS:The aim of this work was to estimate the life expectancy (LE) and disability-free life expectancy (DFLE) for adults with and without diabetes. METHODS:The Chiang method and the adapted Sullivan method were used to estimate LE and DFLE by age and sex. Mortality data in 2011 were available from the Natio...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-016-3948-x

    authors: Huo L,Shaw JE,Wong E,Harding JL,Peeters A,Magliano DJ

    更新日期:2016-07-01 00:00:00

  • Altered immunoreactivity of islet amyloid polypeptide (IAPP) may reflect major modifications of the IAPP molecule in amyloidogenesis.

    abstract::We have developed a mouse monoclonal antibody against rat/mouse islet amyloid polypeptide (IAPP). The antibody recognises an epitope in the N-terminal part of the molecule, which is conserved between different species. The antibody immunohistochemically labelled beta cells in normal islets of most different mammalian ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050751

    authors: Ma Z,Westermark GT,Li ZC,Engström U,Westermark P

    更新日期:1997-07-01 00:00:00

  • Report from the International Pancreas Transplant Registry.

    abstract::From December, 1966 through 1990, 3082 pancreas transplants were reported to the International Registry. A detailed analysis was performed on the 2087 transplants in the 1986-90 data base; during this time the overall one year recipient and graft functional survival rates were 89% and 62%. Univariate analyses showed g...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00587615

    authors: Sutherland DE

    更新日期:1991-08-01 00:00:00

  • Visceral fat and beta cell function in non-diabetic humans.

    abstract:AIMS/HYPOTHESIS:Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial. METHODS:In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m2), we measured VAT and subcutaneous ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1891-3

    authors: Gastaldelli A,Sironi AM,Ciociaro D,Positano V,Buzzigoli E,Giannessi D,Lombardi M,Mari A,Ferrannini E

    更新日期:2005-10-01 00:00:00

  • Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort.

    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

    authors: Gellen B,Thorin-Trescases N,Thorin E,Gand E,Sosner P,Brishoual S,Rigalleau V,Montaigne D,Javaugue V,Pucheu Y,Gatault P,Piguel X,Hadjadj S,Saulnier PJ,SURDIAGENE Study group.

    更新日期:2020-05-01 00:00:00

  • Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.

    abstract:AIMS/HYPOTHESIS:In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macrovascular risk factors (hypertension, ...

    journal_title:Diabetologia

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00125-010-1883-9

    authors: Jacobson AM,Ryan CM,Cleary PA,Waberski BH,Weinger K,Musen G,Dahms W,Diabetes Control and Complications Trial\/EDIC Research Group.

    更新日期:2011-02-01 00:00:00

  • Purchase of antidepressant agents by patients with type 1 diabetes is associated with increased mortality rates in women but not in men.

    abstract:AIMS/HYPOTHESIS:Individuals with diabetes have increased mortality rates compared with the general population. In patients with type 2 diabetes depression further contributes to the increased mortality. Depression and mortality rates in patients with type 1 diabetes are an understudied phenomenon. We therefore studied ...

    journal_title:Diabetologia

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00125-011-2347-6

    authors: Ahola AJ,Harjutsalo V,Saraheimo M,Forsblom C,Groop PH,FinnDiane Study Group.

    更新日期:2012-01-01 00:00:00

  • Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus.

    abstract::The antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences were found between diabetic pat...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00292541

    authors: Diepersloot RJ,Bouter KP,Beyer WE,Hoekstra JB,Masurel N

    更新日期:1987-06-01 00:00:00

  • The association between the IFIH1 locus and type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:We set out to validate a recently reported type 1 diabetes association from the IFIH1 gene variation in an independent cohort from a population of mixed European descent. METHODS:We genotyped five single-nucleotide polymorphisms in the IFIH1 locus, i.e. rs2111485, rs1990760, rs3747517, rs17783344 and r...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-007-0895-6

    authors: Qu HQ,Marchand L,Grabs R,Polychronakos C

    更新日期:2008-03-01 00:00:00

  • Direct effect of GLP-1 infusion on endogenous glucose production in humans.

    abstract:AIMS/HYPOTHESIS:Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusio...

    journal_title:Diabetologia

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00125-012-2738-3

    authors: Seghieri M,Rebelos E,Gastaldelli A,Astiarraga BD,Casolaro A,Barsotti E,Pocai A,Nauck M,Muscelli E,Ferrannini E

    更新日期:2013-01-01 00:00:00