Unique features of β-cell metabolism are lost in type 2 diabetes.

Autor: Muñoz F; Clinical Research Center, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund, Sweden., Fex M; Clinical Research Center, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund, Sweden., Moritz T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Mulder H; Clinical Research Center, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund, Sweden., Cataldo LR; Clinical Research Center, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund, Sweden.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Jun; Vol. 240 (6), pp. e14148. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1111/apha.14148
Abstrakt: Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell type-specific manner; for instance, the glucose activating hexokinase IV enzyme or Glucokinase (GCK), whereas other genes are selectively "disallowed", including lactate dehydrogenase A (LDHA) and monocarboxylate transporter 1 (MCT1). This selective gene program equips β cells with a unique metabolic apparatus to ensure that nutrient metabolism is coupled to appropriate insulin secretion, thereby avoiding hyperglycemia, as well as life-threatening hypoglycemia. Unlike most cell types, β cells exhibit specialized bioenergetic features, including supply-driven rather than demand-driven metabolism and a high basal mitochondrial proton leak respiration. The understanding of these unique genetically programmed metabolic features and their alterations that lead to β-cell dysfunction is crucial for a comprehensive understanding of T2D pathophysiology and the development of innovative therapeutic approaches for T2D patients.
(© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze: MEDLINE
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