Abstract. Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from intestinal L cells upon nutrients ingestion, and is currently used for treating diabetes mellitus. It plays an important role in receptor modulation and cross talk with insulin at the coronary endothelium (CE) and cardiomyocytes (CM) in diabetic type 1 rat heart model. We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation. The binding affinity of GLP-1 to its receptor on CE and CM was calculated using a rat heart perfusion model with [125 I]-GLP-1(7-36). Tissue samples from the heart were used for immunostaining and Western blot analyses. GLP-1 systemic blood levels were measured using ELISA. GLP-1 binding affinity (τ) increased on the CE (0.33 ± 0.01 vs. 0.25 ± 0.01 min; p < 0.001) and decreased on the CM (0.29 ± 0.02 vs. 0.43 ± 0.02 min; p < 0.001) in the diabetic non-treated rats when compared to normal. There was normalization of τ back to baseline on the CE and CM levels with insulin and DPP-IV inhibitor treatment, respectively. Histological sections and immunofluorescence showed receptor upregulation in diabetic rats with significant decrease and even normalization with the different treatment strategies. Systemic GLP-1 levels increased after 14 days of diabetes induction (10 ± 3.7 vs. 103 ± 58 pM; p = 0.0005). In conclusion, there is a significant GLP-1 receptor affinity modulation on the CE and CM levels in rats with diabetes type 1, and a cross talk with GLP-1 analogues in early prevention of cardiac remodeling.

INTRODUCTIONIn Lebanon, the tobacco control policy, Law 174, became effective in 2011. Using the International Tobacco Control Policy Evaluation Project (ITC) conceptual model, this study aims to assess the association between exposure to control measures related to the policy and the intention to quit, which is a mediator in the pathway leading to behavioral change (quitting).METHODSThis is a secondary data analysis of 154 cigarette smokers from a cross-sectional survey that assessed compliance with Law 174 among Beirut residents aged 15–65 years. Data were collected face-to-face, three months after the implementation of indoor public places and tobacco advertisement/promotion bans. Intention to quit smoking was the main outcome. Exposure to policy control measures such as seeing smokers in restaurants, and noticing warning labels on cigarette packs were the explanatory variables. Sociodemographics, past smoking behavior, and psychosocial variables were also considered for their moderating and mediating effects, respectively. Crude and adjusted odds ratios (ORs) were generated. Sobel test was used to check for possible mediation.RESULTSIntention to quit was reported by 24% of cigarette smokers. The association between noticing warning labels and having intentions to quit was statistically significant (adjusted OR=6.27). Concerns about influencing children’s smoking behavior had a statistically significant mediation effect on the relationship. After adding the interaction term between noticing the warnings and previous quit attempts, the OR was inflated to 12.92, suggesting a possible interaction.CONCLUSIONSThis study offers preliminary insight into how Lebanese smokers are influenced by policy related control measures like health warning labels on cigarette packs. Tobacco control policy advocates should push for stronger enforcement of public smoking bans in general. Behavioral intervention should work on the mediator variables to influence smoking behavior and encourage quitting. Further prospective studies modelling quitting as outcome are needed.

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1. Our results showed that insulin treatment of nondiabetic female rats decreased blood glucose level but did not affect nondiabetic male rats. In both male and female diabetic rats, insulin did not completely decrease blood glucose level. Insulin treatment decreased PepT1 mRNA level in nondiabetic male rats and increased mRNA level in nondiabetic female rats without affecting the PepT1 protein level in either sex. Inducing diabetes with STZ increased PepT1 mRNA and protein levels in female rats; however, in diabetic male rats, the increase in mRNA level was accompanied by a decrease in PepT1 protein level. Treatment of diabetic male rats with insulin partially reversed the effect of diabetes on PepT1 mRNA and protein levels, whereas the same treatment completely restored both PepT1 mRNA and protein to control levels in insulin-treated diabetic female rats. In both nondiabetic male and female rats, insulin treatment had no effect on PepT1 influx rate, and STZ treatment decreased the transporter influx rate. Treatment of diabetic male and female rats with insulin significantly increased PepT1 influx rate; however, complete recovery was found only in diabetic female rats. These results clearly show that insulin and diabetes affected blood glucose level as well as PepT1 activity, expression, and protein levels in a sex-dependent manner. These results suggest that a factor, probably estrogen, could be responsible for the sex-dependent effects of diabetes and insulin in PepT1 level and activity.

This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant tau = 1/k-n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. The results showed that diabetes (D) decreased the tau value on the coronary endothelium and increased it on cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased tau on the coronary endothelium only. On the coronary endothelium, tau values of DI and DIDp were normalized. Western blots of the insulin receptor showed upregulation in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4.