480 results match your criteria islet glucokinase

SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux.

Theranostics 2021 4;11(10):4825-4838. Epub 2021 Mar 4.

Department of Endocrine and Metabolic Diseases/ Shanghai institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Sirtuins are NAD-dependent protein deacylases known to have protective effects against age-related diseases such as diabetes, cancer, and neurodegenerative disease. SIRT2 is the only primarily cytoplasmic isoform and its overall role in glucose homeostasis remains uncertain. SIRT2-knockout (KO) rats were constructed to evaluate the role of SIRT2 in glucose homeostasis. Read More

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Genetic activation of α-cell glucokinase in mice causes enhanced glucose-suppression of glucagon secretion during normal and diabetic states.

Mol Metab 2021 Feb 19;49:101193. Epub 2021 Feb 19.

Institute of Diabetes, Obesity, and Metabolism, Perelman School of Medicine, The University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, The University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address:

Objective: While the molecular events controlling insulin secretion from β-cells have been documented in detail, the exact mechanisms governing glucagon release by α-cells are understood only partially. This is a critical knowledge gap, as the normal suppression of glucagon secretion by elevated glucose levels fails in type 2 diabetes (T2D) patients, contributing to hyperglycemia through stimulation of hepatic glucose production. A critical role of glycolytic flux in regulating glucagon secretion was supported by recent studies in which manipulation of the activity and expression of the glycolytic enzyme glucokinase altered the setpoint for glucose-suppression of glucagon secretion (GSGS). Read More

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February 2021

The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice.

Chin J Nat Med 2020 Nov;18(11):827-836

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Key laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address:

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. Read More

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November 2020

Low-Frequency Genetic Variant in the Hepatic Glucokinase Gene Is Associated With Type 2 Diabetes and Insulin Resistance in Chinese Population.

Diabetes 2021 Mar 9;70(3):809-816. Epub 2020 Dec 9.

Departments of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center, Beijing, China

Glucokinase (GCK) regulates insulin secretion and hepatic glucose metabolism, and its inactivating variants could cause diabetes. We aimed to evaluate the association of a low-frequency variant of GCK (rs13306393) with type 2 diabetes (T2D), prediabetes, or both (impaired glucose regulation [IGR]) in a Chinese population. An association study was first conducted in a random cluster sampling population (sample 1: 537 T2D, 768 prediabetes, and 1,912 control), and then another independent population (sample 2: 3,896 T2D, 2,301 prediabetes, and 868 control) was used to confirm the findings in sample 1. Read More

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Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity.

Diabetologia 2020 10 7;63(10):1990-1998. Epub 2020 Sep 7.

Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper understanding of the coupling mechanisms that link glucose metabolism in these cells to the control of insulin secretion is therefore likely to be essential to develop new therapies. Beta cells display a remarkable metabolic specialisation, expressing high levels of metabolic sensing enzymes, including the glucose transporter GLUT2 (encoded by SLC2A2) and glucokinase (encoded by GCK). Read More

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October 2020

Glucosamine potentiates the differentiation of adipose-derived stem cells into glucose-responsive insulin-producing cells.

Ann Transl Med 2020 Apr;8(8):561

College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.

Background: Islet transplantation might be a logical strategy to restore insulin secretion for the treatment of diabetes, however, the scarcity of donors poses an obstacle for such a treatment. As an alternative islet source, differentiation of stem cells into insulin-producing cells (IPCs) has been tried. Many protocols have been developed to improve the efficiency of differentiation of stem cells into IPCs. Read More

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Angiotensin-(1-7) Improves Islet Function in a Rat Model of Streptozotocin- Induced Diabetes Mellitus by Up-Regulating the Expression of Pdx1/Glut2.

Endocr Metab Immune Disord Drug Targets 2021 ;21(1):156-162

Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Objective: To observe the effects of angiotensin-(1-7) (Ang-(1-7)) on glucose metabolism, islet function and insulin resistance in a rat model of streptozotocin-induced diabetes mellitus (DM) and investigate its mechanism.

Methods: Thirty-four male Wistar rats were randomly divided into 3 groups: control group, which was fed a standard diet, DM group, high-fat diet and injected with streptozotocin, and Ang-(1-7) group receiving an injection of streptozotocin followed by Ang-(1-7) treatment. Blood glucose level, fasting serum Ang II and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Read More

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January 2021

Reducing Glucokinase Activity to Enhance Insulin Secretion: A Counterintuitive Theory to Preserve Cellular Function and Glucose Homeostasis.

Front Endocrinol (Lausanne) 2020 9;11:378. Epub 2020 Jun 9.

Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens OH, United States.

Pancreatic beta-cells are the only cells in the body that can synthesize and secrete insulin. Through the process of glucose-stimulated insulin secretion, beta-cells release insulin into circulation, stimulating GLUT4-dependent glucose uptake into peripheral tissue. Insulin is normally secreted in pulses that promote signaling at the liver. Read More

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G6PC2 confers protection against hypoglycemia upon ketogenic diet feeding and prolonged fasting.

Mol Metab 2020 11 20;41:101043. Epub 2020 Jun 20.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address:

Objective: G6PC2 is predominantly expressed in pancreatic islet beta cells. G6PC2 hydrolyzes glucose-6-phosphate to glucose and inorganic phosphate, thereby creating a futile substrate cycle that opposes the action of glucokinase. This substrate cycle determines the sensitivity of glucose-stimulated insulin secretion to glucose and hence regulates fasting blood glucose (FBG) but not fasting plasma insulin (FPI) levels. Read More

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November 2020

Recent clinical advances of glucokinase activators in the treatment of diabetes mellitus type 2.

Pharmazie 2020 06;75(6):230-235

Center for New Drug Evaluation, School of Pharmaceutical Sciences, Shandong University, Jinan, China;, Email:

Glucokinase (GK) is an isozyme of hexokinase that catalyzes the phosphorylation of glucose. GK is present in many organs of the human body, including the liver and pancreas. GK plays an important role in promoting the synthesis of hepatic glycogen and balancing postprandial blood glucose. Read More

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Update on clinical screening of maturity-onset diabetes of the young (MODY).

Diabetol Metab Syndr 2020 8;12:50. Epub 2020 Jun 8.

Disciplina de Endocrinologia, Centro de Diabetes, Universidade Federal de São Paulo (UNIFESP), Rua Estado de Israel, 639-Vila Clementino, São Paulo, SP CEP: 04022-001 Brazil.

Background: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, being characterized by beta-cell disfunction, early onset, and autosomal dominant inheritance. Despite the rapid evolution of molecular diagnosis methods, many MODY cases are misdiagnosed as type 1 or type 2 diabetes. High costs of genetic testing and limited knowledge of MODY as a relevant clinical entity are some of the obstacles that hinder correct MODY diagnosis and treatment. Read More

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Rare causes of hypoglycemia in adults.

Ann Endocrinol (Paris) 2020 Jun 10;81(2-3):110-117. Epub 2020 Apr 10.

Endocrinology, diabetology, metabolism department, Lille university hospital, Lille, France; Inserm U1190 translational research in diabetes, Lille, France; European genomic institute for diabetes EGID, Lille, France. Electronic address:

Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Read More

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[A three-year follow-up observation of a pedigree of maturity onset diabetes of the young caused by a novel mutation of glucokinase and literature review].

Zhonghua Nei Ke Za Zhi 2020 May;59(5):366-371

Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Key Laboratory of Endocrinology of National Health Commission, Beijing 100730, China.

To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK). The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. Read More

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Influence of Cannabinoid Receptor Deficiency on Parameters Involved in Blood Glucose Regulation in Mice.

Int J Mol Sci 2020 Apr 30;21(9). Epub 2020 Apr 30.

Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther, University Halle-Wittenberg, 06108 Halle (Saale), Germany.

Cannabinoids are known to influence hormone secretion of pancreatic islets via G protein‑coupled cannabinoid receptor type 1 and 2 (CB and CB). The present study was designed to further investigate the impact of cannabinoid receptors on the parameters involved in insulin secretion and blood glucose recognition. To this end, CB and CB receptor knockout mice (10-12 week old, both sexes) were characterised at basal state and compared to wild-type mice. Read More

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Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose.

J Mol Endocrinol 2020 05;64(4):235-248

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

The G6PC1, G6PC2 and G6PC3 genes encode distinct glucose-6-phosphatase catalytic subunit (G6PC) isoforms. In mice, germline deletion of G6pc2 lowers fasting blood glucose (FBG) without affecting fasting plasma insulin (FPI) while, in isolated islets, glucose-6-phosphatase activity and glucose cycling are abolished and glucose-stimulated insulin secretion (GSIS) is enhanced at submaximal but not high glucose. These observations are all consistent with a model in which G6PC2 regulates the sensitivity of GSIS to glucose by opposing the action of glucokinase. Read More

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Bee wax coated water-soluble fraction of bee venom improved altered glucose homeostasis in streptozotocin-induced diabetic rats.

J Tradit Chin Med 2019 12;39(6):842-852

Department of Biology Education, College of Education, Chungbuk National University, Cheongju 28644, Republic of Korea.

Objective: To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-soluble fraction of bee venom (BWCBVA) drug over orally administered bee wax (BW) and intraperitoneally administered whole bee venom (BV) in streptozotocin (STZ)-induced diabetic rats.

Methods: Diabetes induced by intraperitoneal administration of 60 mg/kg STZ was treated with BWCBVA, BW, and BV for 21 d. The biochemical, protein and histological changes, and physical characteristics of BWCBVA were then analyzed. Read More

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December 2019

[Effects of on the Proliferation, Apoptosis and Insulin Secretion of Rat Islet Cell Tumor Cells].

Sichuan Da Xue Xue Bao Yi Xue Ban 2020 Jan;51(1):13-17

Department of Public Health Laboratory Sciences, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the effects of ( ) on the proliferation, apoptosis and insulin secretion of rat pancreatic islet cell tumor cells (INS-1).

Methods: INS-1 cells were divided into three groups, normal, repair, and protect groups, and subsequently every group was subjected with metabolites, live orpasteurized for 48 h. A group that did not treat with anything was set as blank control. Read More

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January 2020

How Heterogeneity in Glucokinase and Gap-Junction Coupling Determines the Islet [Ca] Response.

Biophys J 2019 12 5;117(11):2188-2203. Epub 2019 Nov 5.

Department of Bioengineering, University of Colorado, Aurora, Colorado; Barbara Davis Center for Childhood Diabetes, Anschutz Medical Campus, University of Colorado, Aurora, Colorado. Electronic address:

Understanding how cell subpopulations in a tissue impact overall system function is challenging. There is extensive heterogeneity among insulin-secreting β-cells within islets of Langerhans, including their insulin secretory response and gene expression profile, and this heterogeneity can be altered in diabetes. Several studies have identified variations in nutrient sensing between β-cells, including glucokinase (GK) levels, mitochondrial function, or expression of genes important for glucose metabolism. Read More

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December 2019

Genetic deletion of a short fragment of glucokinase in rabbit by CRISPR/Cas9 leading to hyperglycemia and other typical features seen in MODY-2.

Cell Mol Life Sci 2020 Aug 13;77(16):3265-3277. Epub 2019 Nov 13.

Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun, 130062, China.

Glucokinase (GCK) is a key enzyme in glucose sensing and glycemic regulation. In humans, mutations in the GCK gene cause maturity-onset diabetes of the young 2 (MODY-2), a disease that is characterized by an early-onset and persistent hyperglycemia. It is known that Gck knockout (KO) is lethal in mice with Gck KO mice dying within 2 weeks after birth. Read More

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Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study.

Diabetes Care 2020 01 8;43(1):82-89. Epub 2019 Nov 8.

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K.

Objective: Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. Read More

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January 2020

Newer perspective on the coupling between glucose-mediated signaling and β-cell functionality.

Endocr J 2020 Jan 6;67(1):1-8. Epub 2019 Nov 6.

Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Insulin secretion by the pancreatic β-cells is elicited in response to elevated extracellular glucose concentration. In addition to triggering insulin secretion, glucose-induced signal regulates β-cell proliferation and survival. However, the molecular mechanism underlying the effects of glucose on the β-cell functionality still remains unclear. Read More

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January 2020

Effects of Pterostilbene on Diabetes, Liver Steatosis and Serum Lipids.

Curr Med Chem 2021 ;28(2):238-252

Nutrition and Obesity Group, Department of Pharmacy and Food Sciences, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria, Spain.

Pterostilbene, a phenolic compound derived from resveratrol, possesses greater bioavailability than its parent compound due to the presence of two methoxyl groups. In this review, the beneficial effects of pterostilbene on diabetes, liver steatosis and dyslipidemia are summarized. Pterostilbene is a useful bioactive compound in preventing type 1 diabetes, insulin resistance and type 2 diabetes in animal models. Read More

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February 2021

Metabolic and Functional Heterogeneity in Pancreatic β Cells.

J Mol Biol 2020 03 13;432(5):1395-1406. Epub 2019 Aug 13.

Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, United Kingdom; Lee Kong Chian School of Medicine, Nan Yang Technological University, Singapore.

Metabolic and secretory heterogeneity are fundamental properties of pancreatic islet β cells. Emerging data suggest that stable differences in the transcriptome and proteome of individual cells may create cellular hierarchies, which, in turn, establish coordinated functional networks. These networks appear to govern the secretory activity of the whole islet and be affected in some forms of diabetes mellitus. Read More

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Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

Diabet Med 2019 12 25;36(12):1694-1702. Epub 2019 Jul 25.

Departments of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

Aim: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population.

Methods: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. Read More

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December 2019

Therapeutic effects of ethanolic extract from the green cocoon shell of silkworm on type 2 diabetic mice and its hypoglycaemic mechanism.

Toxicol Res (Camb) 2019 May 26;8(3):407-420. Epub 2019 Feb 26.

Silk Biotechnology Laboratory , School of Biology and Basic Medical Sciences , Soochow University , China . Email:

Diabetes mellitus is a clinically complex disease characterized by hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism. The aim of this study was to determine the therapeutic effect of ethanolic extract (EE) from the green cocoon sericin layer of silkworm on mice with type 2 diabetes mellitus (T2DM) and its hypoglycaemic mechanisms. The results showed that oral EE for 7 weeks had significant ameliorative effects on all the biochemical parameters studied . Read More

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Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets.

Physiol Rep 2018 10;6(20):e13907

Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

Rodent islets are widely used to study the pathophysiology of beta cells and islet function, however, structural and functional differences exist between human and rodent islets, highlighting the need for human islet studies. Human islets are highly variable, deteriorate during culture, and are difficult to genetically modify, making mechanistic studies difficult to conduct and reproduce. To overcome these limitations, we tested whether pseudoislets, created by dissociation and reaggregation of islet cell suspensions, allow for assessment of dynamic islet function after genetic modulation. Read More

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October 2018

Reducing Glucokinase Activity Restores Endogenous Pulsatility and Enhances Insulin Secretion in Islets From db/db Mice.

Endocrinology 2018 11;159(11):3747-3760

Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio.

An early sign of islet failure in type 2 diabetes (T2D) is the loss of normal patterns of pulsatile insulin release. Disruptions in pulsatility are associated with a left shift in glucose sensing that can cause excessive insulin release in low glucose (relative hyperinsulinemia, a hallmark of early T2D) and β-cell exhaustion, leading to inadequate insulin release during hyperglycemia. Our hypothesis was that reducing excessive glucokinase activity in diabetic islets would improve their function. Read More

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November 2018

Beta-cell hubs maintain Ca oscillations in human and mouse islet simulations.

Islets 2018 ;10(4):151-167

b Department of Computer Science , University of Oxford , Oxford , UK.

Islet β-cells are responsible for secreting all circulating insulin in response to rising plasma glucose concentrations. These cells are a phenotypically diverse population that express great functional heterogeneity. In mice, certain β-cells (termed 'hubs') have been shown to be crucial for dictating the islet response to high glucose, with inhibition of these hub cells abolishing the coordinated Ca oscillations necessary for driving insulin secretion. Read More

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Complications of Diabetes: An Insight into Genetic Polymorphism and Role of Insulin.

Recent Pat Inflamm Allergy Drug Discov 2018 ;12(1):78-86

Department of Law, Govt. College University, Faisalabad, Pakistan.

Background: Diabetes Mellitus (DM) is an advanced and chronic endocrine disorder characterized by an insufficiency of insulin secretion from pancreatic β-cells and liver, adipose tissues, and skeletal muscles.

Objective: The main objective of this study is to understand the mechanism and genes which are responsible for the prevalence of diabetes. The study also covers various types of diabetic complications with special reference to insulin role and defects. Read More

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December 2018

Expression of miR-206 in human islets and its role in glucokinase regulation.

Am J Physiol Endocrinol Metab 2018 10 10;315(4):E634-E637. Epub 2018 Jul 10.

NHMRC Clinical Trials Centre, The University of Sydney , New South Wales , Australia.

Inappropriate insulin secretion from β-cells is considered as an early sign of impaired glucose tolerance and type 2 diabetes (T2D). Glucokinase (GCK) is an important enzyme that regulates glucose metabolism and ensures that the normal circulating glucose concentrations are maintained. GCK expression is induced by glucose and regulated via transcription factors and regulatory proteins. Read More

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October 2018