Here are summaries of two seminal papers in the field of beta cells in diabetes, along with links to more complete versions.
β-cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
Philippe A. Halban, Kenneth S. Polonsky, Donald W. Bowden, Meredith A. Hawkins, Charlotte Ling, Kieren J. Mather, Alvin C. Powers, Christopher J. Rhodes, Lori Sussel, and Gordon C. Weir Department of Genetic Medicine and Development (P.A.H.), University of Geneva, Switzerland; Department of Medicine, Section of Endocrinology (K.S.P.), University of Chicago, Chicago, IL 60637; Center for Genomics and Personalized Medicine Research and Center for Diabetes Research (D.W.B.), Wake Forest University, Winston-Salem, NC 27106; Department of Medicine (Endocrinology) and Global Diabetes Institute, (M.A.H.), Albert Einstein College of Medicine, Bronx, NY 10461; Department of Clinical Sciences (C.L.), Lund University, Lund, Sweden; Department of Endocrinology (K.J.M.), IN University, Indianapolis, IN 46202; Division of Diabetes, Endocrinology and Metabolism (A.C.P.), Vanderbilt University School of Medicine, Nashville, TN 37232; Kovler Diabetes Center, Department of Medicine (C.J.R.), University of Chicago, Chicago, IL 60637; Naomi Berrie Diabetes Center (L.S.), Columbia University, NY, NY 10027; and Joslin Diabetes Center (G.C.W), Harvard Medical School, Boston, MA 02215
Objective: This report examines the foundation of β-cell failure in type 2 diabetes and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment.
Participants: A group of experts participated in a conference on October 14–16, 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations.
Evidence: The writing group based this report on conference presentations, discussion,and debate. Topics covered include genetic predisposition, the foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions.
Conclusions: β-cell failure is central to the development and progression of type 2 diabetes. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include: 1) Impact the natural history of β-cell failure; 2) Identify and characterize genetic loci for type 2 diabetes; 3) Target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) Develop alternative sources of β-cells for cell-based therapy; 5) Focus on metabolic environment to provide indirect benefit to β-cells; 6) Improve understanding of the physiology of responses to bypass surgery; 7) Identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.
View full article (PDF) at Journal of Clinical Endocrinology & Metabolism
Targeting Beta-Cell Function Early in the Course of Therapy for Type 2 Diabetes Mellitus
Jack L. Leahy, MD
Irl B. Hirsch, MD
Kevin A. Peterson, MD, MPH
Doron Schneider, MD
From a consensus statement recently published in the Journal of Clinical Endocrinology & Metabolism
Traditionally, Type 2 diabetes mellitus (T2DM) is viewed as a progressive disease. Pathogenesis is complex, characterized by genetic predisposition that—together with metabolic abnormalities associated with body-weight gain, defective insulin secretion and action, and elevated endogenous glucose production—eventually compromise glucose homeostasis (1). Evidence from both human and animal studies suggests that T2DM is characterized by decreased functional β-cell mass that cannot adapt insulin secretion to compensate for increasing insulin resistance driving the development of overt T2DM (2, 3). β-cell function continues declining progressively despite treatment with anti-diabetic medications as well, as highlighted in the 1995 United Kingdom Prospective Diabetes Study (4).
Accumulating evidence suggests this decline may be slowed or even reversed, particularly in early stages of disease (5). Furthermore, new therapeutic classes of diabetes medications act to improve β-cell function, thus potentially altering the course of the disease. The precise role these new therapies might play in treating T2DM, however, has not yet been fully addressed. In fact, despite the primary and pivotal role that β-cells appear to play in disease development and progression, current clinical practice remains heavily focused on insulin resistance.