The influence of rare genetic variation in SLC30A8 on diabetes incidence and β-cell function

Liana K Billings1, Kathleen A Jablonski, Rachel J Ackerman

  • 1Center for Human Genetic Research (L.K.B., R.J.A., A.T., R.R.F., J.B.M., J.C.F.) and Diabetes Research Center (Diabetes Unit) (L.K.B., L.M.D., J.C.F.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; Department of Medicine (L.K.B., L.M.D., J.C.F.), Harvard Medical School, and Department of Nutrition (P.W.F.), Harvard School of Public Health, Boston, Massachusetts 02115; Department of Medicine (L.K.B.), NorthShore University HealthSystem, Evanston, Illinois 60201; University of Chicago (L.K.B.), Pritzker School of Medicine, Chicago, Illinois 60637; The Biostatistics Center (K.A.J.), George Washington University, Rockville, Maryland 20852; Program in Medical and Population Genetics (A.T., J.B.M., C.G., J.C.F.), Broad Institute, Cambridge, Massachusetts 02142; Department of Epidemiology (D.D.), Colorado School of Public Health, University of Colorado, Denver, Colorado 80045; Division of Metabolism, Endocrinology, and Nutrition (S.E.K.), VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108; Department of Clinical Sciences (P.W.F.), Genetic and Molecular Epidemiology Unit, Lund University, SE-200 41 Malmö, Sweden; Diabetes Epidemiology and Clinical Research Section (R.L.H., W.C.K.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85014; Department of Medicine (N.M.M.), Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Medicine (A.R.S.), Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Nutrition (E.J.M.-D.), University of North Carolina, Gillings School of Global Public Health, Chapel Hill, North Carolina 27599.

Abstract

Related Concept Videos

Type II Diabetes I: Introduction01:26

Type II Diabetes I: Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
17
Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular...
75
Type I Diabetes I: Introduction01:12

Type I Diabetes I: Introduction

Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.Autoimmune Destruction of β-CellsThe hallmark of type 1...
45
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
189
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
28
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
15.2K