Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

Characteristics of blood glucose excursions in type 2 diabetes mellitus patients with three different Traditional Chinese Medicine syndromes

OBJECTIVE:To explore the characteristics of blood glucose excursions of type 2 diabetes mellitus patients with three different Traditional Chinese Medicine(TCM) syndromes.METHODS:One hundred and nine patients with type 2 diabetes mellitus were recruited from the Department of Endocrinology and the Department of TCM of the Sixth People's Hospital affiliated to Shanghai Jiao Tong University.Subjects were divided into three groups according to TCM syndrome:intrinsic Damp(n- 42),Yin deficiency and internal Heat(n = 25),and Qi and Yin deficiency(n- 42).Subcutaneous interstitial glucose was monitored with a continuous glucose monitoring system for 3consecutive days to investigate the glycemic profile in each group.Plasma C-peptide levels were measured,and an arginine test was taken in 10 patients randomly selected from each group.Glucose data and glycemic variability were analyzed to investigate the differences among the groups.The change in C-peptide levels and the results from arginine trial were used to evaluate β cell function.RESULTS:Indicators reflecting blood glucose level were the highest in subjects with Yin deficiency and internal Heat syndrome,and parameters reflecting glycemic variability were the lowest in those with Qi and Yin deficiency syndrome.The change in C-peptide levels showed that subjects with Qi and Yin deficiency syndrome had the best βcell function among the three groups;this was confirmed by the arginine trial.CONCLUSION:Patients with Qi and Yin deficiency syndrome had a more stable blood glucose profile,as glycemic variability was higher in those with intrinsic Damp syndrome and those with Yin deficiency and internal Heat syndrome.

Effects of Mo-Rubbing abdomen manipulation on glucose metabolism and inflammatory factors in rats with type 2 diabetes mellitus

Objective To observe the effect of Mo-Rubbing abdomen manipulation on glucose metabolism and inflammatory factors in rats with type 2 diabetes mellitus(T2DM).Methods Sixty Sprague-Dawley rats were randomly divided into a normal group(n=10)and a group for modeling(n=50)using the random number table method.Rats in the group for modeling were induced to form T2DM models by a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin.Thirty successfully modeled rats were randomly divided into a model group,a Mo-Rubbing abdomen group,and a metformin group,with 10 rats in each group.Rats in the normal group and the model group received no intervention,those in the Mo-Rubbing abdomen group received Mo-Rubbing abdomen manipulation,and those in the metformin group received metformin by gavage.After 8-week intervention,fasting insulin(FINS),fasting plasma glucose(FPG),homeostasis model assessment for insulin resistance(HOMA-IR)and area under the curve at the oral glucose tolerance test(AUC-OGTT),as well as serum inflammatory factors interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-αwere detected,and the morphological changes of the pancreas were also observed.Results After the 8-week intervention,the levels of FINS,FPG,HOMA-IR,and AUC-OGTT of rats in the Mo-Rubbing abdomen group were significantly lower than those in the model group(P<0.05);the pancreatic injury degree in the Mo-Rubbing abdomen group and the metformin group was lower than that in the model group.Compared with the model group,the serum IL-1β,IL-6,and TNF-αlevels of rats in the Mo-Rubbing abdomen group were significantly decreased(P<0.05),and the serum IL-1βand TNF-αlevels of the metformin group showed a downward trend;the serum IL-6 and TNF-αlevels in the Mo-Rubbing abdomen group were significantly lower than those in the metformin group(P<0.01).There was a significant positive correlation between FPG with IL-1β,IL-6,and TNF-αin the T2DM rats(P<0.01).Conclusion Mo-Rubbing abdomen manipulation reduces the inflammatory response and improves the morphological changes of the pancreas in T2DM rats,thereby achieving the effect of lowering blood glucose.