Analysis Tools
homeostasis/metabolism
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• impaired mitophagy flux in pancreatic beta cells
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• reduction in the number of LC3+ puncta co-stained with the lysosome-specific dye Lysotracker (reflecting the presence of autophagolysosomes) in pancreatic beta cells from 18-day old islets
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• impaired glucose-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• impaired alpha-ketoisocaproic acid (alpha-KIC)-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• normal potassium chloride (KCl)-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• normal islet insulin content in 18-day old mice
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• increased plasma glucose level in the freely-fed state as early as 18 days of age
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• progressive hyperglycemia ultimately leading development of diabetes
• >2-fold elevation of plasma glucose level in the freely-fed state at 50 days of age
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• 75% reduction of plasma insulin level in the freely-fed state at 50 days, but not at 18 days, of age
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endocrine/exocrine glands
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• increased protein abundance of cleaved-caspase 9, but not cleaved-caspase 3, in pancreatic islets
• however, the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2 (BAX:BCL-2) is reduced, suggesting that protective mechanisms may be activated in young mice
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• increased surface density of docked large dense core vesicles (LDCV) in which insulin is packaged in pancreatic beta cells from 18-day old islets
• however, normal volume density of LDCV which reflects total number of insulin granules
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• reduced beta cell mass in diabetic mice at 7 weeks of age
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• reduced islet density in diabetic mice at 7 weeks of age
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• impaired glucose-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• impaired alpha-ketoisocaproic acid (alpha-KIC)-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• normal potassium chloride (KCl)-stimulated insulin secretion in pancreatic islets isolated from both 18-day and 35-day old mice
• normal islet insulin content in 18-day old mice
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cellular
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• increased percentage of mitochondria with vesicular and swollen morphology in pancreatic beta cells isolated from 18-day old islets
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• decreased expression of mitochondrial encoded genes and reduced mitochondrial DNA content in pancreatic islets
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• increased percentage of swollen mitochondria in pancreatic beta cells isolated from 18-day old islets
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• impaired mitophagy flux in pancreatic beta cells
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• reduction in the number of LC3+ puncta co-stained with the lysosome-specific dye Lysotracker (reflecting the presence of autophagolysosomes) in pancreatic beta cells from 18-day old islets
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• increased protein abundance of cleaved-caspase 9, but not cleaved-caspase 3, in pancreatic islets
• however, the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2 (BAX:BCL-2) is reduced, suggesting that protective mechanisms may be activated in young mice
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• increased mRNA expression of ER stress markers (Ddit3 and Cebpb) in pancreatic islets isolated from both 18-day old mice
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• after stimulation with 16.7 mM glucose, maximal decrease in TMRM fluorescence intensity is reduced by 40% in pancreatic islets isolated from 18-day old mice
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