AIMS/HYPOTHESIS: Little information is available on the insulin release properties of pancreatic islets isolated from type 2 diabetic subjects. Since mitochondria represent the site where important metabolites that regulate insulin secretion are generated, we studied insulin release as well as mitochondrial function and morphology directly in pancreatic islets isolated from type 2 diabetic patients. METHODS: Islets were prepared by collagenase digestion and density gradient purification, and insulin secretion in response to glucose and arginine was assessed by the batch incubation method. Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyrosine levels were evaluated and correlated with insulin secretion. RESULTS: Compared to control islets, diabetic islets showed reduced insulin secretion in response to glucose, and this defect was associated with lower ATP levels, a lower ATP/ADP ratio and impaired hyperpolarization of the mitochondrial membrane. Increased protein expression of UCP-2, complex I and complex V of the respiratory chain, and a higher level of nitrotyrosine were also found in type 2 diabetic islets. Morphology studies showed that control and diabetic beta cells had a similar number of mitochondria; however, mitochondrial density volume was significantly higher in type 2 diabetic beta cells. CONCLUSIONS/ INTERPRETATION: In pancreatic beta cells from type 2 diabetic subjects, the impaired secretory response to glucose is associated with a marked alteration of mitochondrial function and morphology. In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release.
AIMS/HYPOTHESIS: Little information is available on the insulin release properties of pancreatic islets isolated from type 2 diabetic subjects. Since mitochondria represent the site where important metabolites that regulate insulin secretion are generated, we studied insulin release as well as mitochondrial function and morphology directly in pancreatic islets isolated from type 2 diabeticpatients. METHODS: Islets were prepared by collagenase digestion and density gradient purification, and insulin secretion in response to glucose and arginine was assessed by the batch incubation method. Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyrosine levels were evaluated and correlated with insulin secretion. RESULTS: Compared to control islets, diabetic islets showed reduced insulin secretion in response to glucose, and this defect was associated with lower ATP levels, a lower ATP/ADP ratio and impaired hyperpolarization of the mitochondrial membrane. Increased protein expression of UCP-2, complex I and complex V of the respiratory chain, and a higher level of nitrotyrosine were also found in type 2 diabetic islets. Morphology studies showed that control and diabetic beta cells had a similar number of mitochondria; however, mitochondrial density volume was significantly higher in type 2 diabetic beta cells. CONCLUSIONS/ INTERPRETATION: In pancreatic beta cells from type 2 diabetic subjects, the impaired secretory response to glucose is associated with a marked alteration of mitochondrial function and morphology. In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release.
Authors: P Marchetti; F Dotta; Z Ling; R Lupi; S Del Guerra; C Santangelo; M Realacci; L Marselli; U Di Mario; R Navalesi Journal: Diabetes Care Date: 2000-05 Impact factor: 19.112
Authors: C Y Zhang; G Baffy; P Perret; S Krauss; O Peroni; D Grujic; T Hagen; A J Vidal-Puig; O Boss; Y B Kim; X X Zheng; M B Wheeler; G I Shulman; C B Chan; B B Lowell Journal: Cell Date: 2001-06-15 Impact factor: 41.582
Authors: C B Chan; D De Leo; J W Joseph; T S McQuaid; X F Ha; F Xu; R G Tsushima; P S Pennefather; A M Salapatek; M B Wheeler Journal: Diabetes Date: 2001-06 Impact factor: 9.461
Authors: Nicolai M Doliba; Wei Qin; Habiba Najafi; Chengyang Liu; Carol W Buettger; Johanna Sotiris; Heather W Collins; Changhong Li; Charles A Stanley; David F Wilson; Joseph Grimsby; Ramakanth Sarabu; Ali Naji; Franz M Matschinsky Journal: Am J Physiol Endocrinol Metab Date: 2011-09-27 Impact factor: 4.310
Authors: Mourad Ferdaoussi; Xiaoqing Dai; Mette V Jensen; Runsheng Wang; Brett S Peterson; Chao Huang; Olga Ilkayeva; Nancy Smith; Nathanael Miller; Catherine Hajmrle; Aliya F Spigelman; Robert C Wright; Gregory Plummer; Kunimasa Suzuki; James P Mackay; Martijn van de Bunt; Anna L Gloyn; Terence E Ryan; Lisa D Norquay; M Julia Brosnan; Jeff K Trimmer; Timothy P Rolph; Richard G Kibbey; Jocelyn E Manning Fox; William F Colmers; Orian S Shirihai; P Darrell Neufer; Edward T H Yeh; Christopher B Newgard; Patrick E MacDonald Journal: J Clin Invest Date: 2015-09-21 Impact factor: 14.808
Authors: I Giannulis; E Mondini; F Cinti; A Frontini; I Murano; R Barazzoni; G Barbatelli; D Accili; S Cinti Journal: Nutr Metab Cardiovasc Dis Date: 2013-10-23 Impact factor: 4.222