| BACKGROUND AND OBJECTIVEGhrelin as the endogenous ligand of the growth hormone secretagogue receptor was found toplay a role in the regulation of energy balance and had been connected to regulation of glucosehomeostasis o Glucagon is a main islet hormone to maintain glucose homeostasis. Studies showthat glucagon inhibits ghrelin secretion in human. In addition, ghrelin has complex interactionswith glucose and other islet hormones like insulin and somatostatin and was found to beassociated with iusulin resistance. Impaired islet function, including the glucagon/insulinimbanlance, and iusulin resistance is considered to be two major pathogenesis of T2DM. Allabove implies that the pathogenesis of T2DM may affect ghrelin and its regulation, and ghrelinmay participate in the pathogenesis of T2DM. This study aims to evaluate the effect of glucagonon ghrelin secretion in T2DM and to investigate the effect of pathogenesis of T2DM on ghrelinand its regulation through administration of exogenous glucagon and evaluation ofβcell functionand insulin resistance.MATERIALS AND METHODSSubjects were healthy and diabetic volunteers who visited to the first affiliated hospital ofShantou University Medical colleage within 2006-5～2006-11.34 diabetic patients including 19males and 15 females, with mean age 51±12 yr and without acute or chronic diabeticcomplications as T2DM group, 21 healthy controls whose age and constituent ratio of sex wascomparatable with T2DM group as NC group was studied. Both groups were without overweightand obesity(BMI 18～25kg/m~2). All subjects were admitted to investigation after an over 8-hourovernight fast and took a measurement for height, weight, AC, SBP, DBP, BFP and BFM first.Venous blood was sampled at fasting and 6min after intravenous injection of 1mg of glucagon formeasurement of glucose, C-peptide, ghrelin, GHbA1c, FMN, TG, TC, HDLc, LDLc, AST, ALTand UA. Plasma ghrelin was measured by ELISA and C-peptide was masured by RIA. The dataacquired was calculated and analysed by software HOMA2 Calculator V2.2, Curve Expert 1.3and SPSS11.0. RESULTS(1)Clinical and laboratory data: AC, GHbAlc and FMN in T2DM group were significantlyhigher than those in NC group(P＜0.05). There was no significant difference in constituent ratioof sex, age, weight, height, BMI, SBP, DBP, BFP, BFM, TG, TC, HDLc, LDLc, AST, ALT andUA (P＞0.05). (2)HOMA Index: HOMA2 IR in T2DM group were significantly higher than inNC group(P=0.031), HOMA2%B in T2DM group were significantly lower than in NC group(P=0.004). (3) Parameters in glucagon test: fasting and 6min glucose level were significantlyhigher than those in NC group(P＜0.001). 6min C-peptide level in T2DM group was significantlylower than in NC group(P＜0.001) There was no significant difference in fasting C-peptied,fasting ghrelin and 6min ghrelin levels between two groups(P＞0.05). Paired-sample T testshowed that after injection of glucagon, glucose and C-peptide were significantly increased inboth groups(P＜0.05), and ghrelin was significantly increased in NC group(P＜0.001) but had nosignificant change in T2DM group(P=0.341). (4)Correlate and regressive analysis: fastingghrelin level were significantly positive correlated with BFM(R=0.301, P=0.025) and BFP(R=0.271, P=0.046) in Pearson correlations. After correcting for BFM, fasting ghrelin level weresignificantly negative correlated with BMI(r=-0.351, P=0.012) in Partial correlations. Inmultivariates regression modle, BFM and BMI were preditors of fasting ghrelin level, andGHbA1c was preditor of percentage change of ghrelin level.CONCLUSIONSThis study showed that ghrelin was accociated with FBM and BMI in normal-weight subjects. Inhealthy subjects glucagon decreased ghrelin and the effect of ghrelin suppression by glucagonwas weaken in T2DM, which implies that peripheral hyperglucagonemia in T2DM was unable tosuppress ghrelin effectively. The efficiency of ghrelin suppression by glucagon was associatedwith status of glucose homeostasis in the whole body, which suggested that the weakenefficiency of ghrelin suppression by glucagon may be associated with the pathogenesis of T2DMincluding impaired islet function and insulin resistance. This change of ghrelin regulation byglucagon may participate in the pathological progress of T2DM. |
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