详细记录  
题名:Quantification of beta-cell insulin secretory function using a graded glucose infusion with C-peptide deconvolution in dysmetabolic, and diabetic cynomolgus monkeys.
作者:WANG X; HANSEN BC; SHI D; FANG Y; DU F; WANG B; CHEN YM; GREGOIRE FM; WANG YX;
来源:Diabetol Metab Syndr. 2013 Jul 25;5(1):40. doi: 10.1186/1758-5996-5-40. [ IF= 0.00 ] ]
URL :10.1186/1758-5996-5-40
日期:20130830
摘要:BACKGROUND: Quantitation of beta-cell function is critical in better
understanding of the dynamic interactions of insulin secretion, clearance and
action at different phases in the progression of diabetes. The present study
aimed to quantify beta-cell secretory function independently of insulin
sensitivity in the context of differential metabolic clearance rates of insulin
(MCRI) in nonhuman primates (NHPs). METHODS: Insulin secretion rate (ISR) was
derived from deconvolution of serial C-peptide concentrations measured during a 5
stage graded glucose infusion (GGI) in 12 nondiabetic (N), 8 prediabetic or
dysmetabolic (DYS) and 4 overtly diabetic (DM) cynomolgus monkeys. The
characterization of the monkeys was based on the fasting glucose and insulin
concentrations, glucose clearance rate measured by intravenous glucose tolerance
test, and insulin resistance indices measured in separate experiments. The molar
ratio of C-peptide/insulin (C/I) was used as a surrogate index of hepatic MCRI.
RESULTS: Compared to the N monkeys, the DYS with normal glycemia and
hyperinsulinemia had significantly higher basal and GGI-induced elevation of
insulin and C-peptide concentrations and lower C/I, however, each unit of
glucose-stimulated ISR increment was not significantly different from that in the
N monkeys. In contrast, the DM monkeys with beta-cell failure and hyperglycemia
had a depressed GGI-stimulated ISR response and elevated C/I. CONCLUSIONS: The
present data demonstrated that in addition to beta-cell hypersecretion of
insulin, reduced hepatic MCRI may also contribute to the development of
hyperinsulinemia in the DYS monkeys. On the other hand, hyperinsulinemia may
cause the saturation of hepatic insulin extraction capacity, which in turn
reduced MCRI in the DYS monkeys. The differential contribution of ISR and MCRI in
causing hyperinsulinemia provides a new insight into the trajectory of beta-cell
dysfunction in the development of diabetes. The present study was the first to
use the GGI and C-peptide deconvolution method to quantify the beta-cell function
in NHPs.

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