ABSTRACT
Glucose-stimulated insulin secretion (GSIS) by pancreatic ß cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood glucose levels and brain glucose distribution in humans. Animal experiments to determine a possible network between the brain and ß cells revealed that fasting-dependent hyperactivation of AMP-activated protein kinase in the hypothalamus inhibited first-phase GSIS by stimulating the ß-adrenergic pancreatic nerve. Furthermore, abnormal excitability of this brain-ß cell neural axis was involved in diabetes-related impairment of first-phase GSIS in diabetic animals. Finally, pancreatic denervation improved first-phase GSIS and glucose tolerance and ameliorated severe diabetes by preventing ß cell loss in diabetic animals. These results indicate that impaired first-phase GSIS is critical for brain distribution of dietary glucose after fasting. Furthermore, ß cells in individuals with diabetes mistakenly sense that they are under conditions that mimic prolonged fasting. The present study provides additional insight into both ß cell physiology and the pathogenesis of ß cell dysfunction in type 2 diabetes.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Diabetes Mellitus, Type 2/metabolism , Fasting/metabolism , Hypothalamus/metabolism , Insulins/metabolism , Animals , Brain/metabolism , Denervation , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/therapy , Disease Models, Animal , Fluorodeoxyglucose F18 , Glucose/metabolism , Glucose Tolerance Test/methods , Humans , Insulin-Secreting Cells/metabolism , Male , Organ Specificity , Pancreas/innervation , Positron-Emission Tomography , Rats , Sympathetic Nervous System/metabolism , Time Factors , Tomography, X-Ray ComputedABSTRACT
Objective To investigate the effect of pancreatic ? cell dysfunction on abnormal glucose tolerance during Graves hyperthyroidism. Methods We investigated 6 healthy people and 36 Graves disease patients with abnormal glucose tolerance, and determined blood sugar and insulin at 0, 60 and 120 minutes after breakfast respectively. Then the HOMA-IR, HOMA-? and ISI were compared between the two groups. Results The HOMA-IR in the Graves disease patients with abnormal glucose tolerance is evidently higher than in the healthy subjects (P
ABSTRACT
Objective To investigate the effects of chronic hyperglycemia on the proliferation,secretion function and expression of endoplasmic reticulum stress(ERS) related molecules in pancreatic ? cell line MIN6. Methods MIN6 cells were treated with different concentrations of glucose(5.6,25 and 33.3mmol/L) and were harvested at indicated time(24h and 96h) for examinations.Cell proliferation was tested using CCK-8 solution,insulin and proinsulin secretion function was determined by ELISA,and mRNA expression of ERS related molecules(Total XBP-1,Spliced XBP-1) and protein expression of phosphorylated IRE1? were detected by Real-time PCR and Western blotting,respectively. Results After treatment with hyperglycemia for 96h, cell proliferation was significantly lower than that treated for 24h(P
ABSTRACT
Objective To establish a pancreatic ?-cell developmet fish model with specific spatial expression patterns.Methods Molecular cloning,microinjection,whole embryo in-situ hybridization(WISH)and fluorescence microscopy in living were used to analyze of ?-cell development through generation of transgenic zebrafish.ResultsScreened and established pancreatic ? cells of transgenic zebrafish,and confirmed the fluorescence protein expression in the same spatiotemporal pattern with endogenous insulin gene to achieve dynamic monitoring islet ?-cell development situation in vivo.Conclusion The pancreatic ? cells of transgenic zebrafish animal model can successfully trace pancreatic ? cell development.
ABSTRACT
ATP-sensitive potassium channels (KATP channels) play important roles in various tissues tinder physiological and pathophysiological condi- conditions by coupling cell metabolic status to electrical activity. The KATP channel is a tetrameric complex of inwardly rectified potassium (Kir) and ATP binding protein (ABP). The Kir subunits form the channel pore, whereas ABP is required for activation and regulation. Both Kir and ABP are divided into different subunits and the various Kir and ABP subunits "mix and match" to form KATP channels with different pharmacological and nucleotide sensitivities. This review focuses on the molecular structure, physiological roles, pathophysiological and pharmacological proper ties of KATP channels in different tissues.
