title: Mitochondrial regulation of β-cell function: maintaining the momentum for insulin release.
abstract: All forms of diabetes share the common etiology of insufficient pancreatic β-cell function to meet peripheral insulin demand. In pancreatic β-cells, mitochondria serve to integrate the metabolism of exogenous nutrients into energy output, which ultimately leads to insulin release. As such, mitochondrial dysfunction underlies β-cell failure and the development of diabetes. Mitochondrial regulation of β-cell function occurs through many diverse pathways, including metabolic coupling, generation of reactive oxygen species, maintenance of mitochondrial mass, and through interaction with other cellular organelles. In this chapter, we will focus on the importance of enzymatic regulators of mitochondrial fuel metabolism and control of mitochondrial mass to pancreatic β-cell function, describing how defects in these pathways ultimately lead to diabetes. Furthermore, we will examine the factors responsible for mitochondrial biogenesis and degradation and their roles in the balance of mitochondrial mass in β-cells. Clarifying the causes of β-cell mitochondrial dysfunction may inform new approaches to treat the underlying etiologies of diabetes.
authors: Division of Cardiology, Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Brett A
authors: BA
authors: Kaufman
authors: Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors: Changhong
authors: C
authors: Li
authors: Division of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors: Scott A
authors: SA
authors: Soleimanpour
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D004272:DNA, Mitochondrial; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D063306:Mitophagy; D009154:Mutation; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004272:DNA, Mitochondrial; D005227:Fatty Acids; D018398:Homeodomain Proteins; D007328:Insulin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; D005973:Glutamine; D005947:Glucose
keywords: Diabetes; Islet; Metabolism; Mitochondria; Mitophagy; mtDNA