Chronic binge alcohol and ovariectomy-mediated impaired insulin responsiveness in SIV-infected female rhesus macaques

Objective: Aging people living with HIV (PLWH), especially post-menopausal women may be at higher risk of comorbidities associated with HIV, ART, hypogonadism and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-β in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX), on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Methods: Female macaques were administered CBA (12-15 g/kg/week) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIVmac251, and initiated on anti-retroviral therapy (ART) 2.5 months post-infection. After one month of ART, macaques were randomized to OVX or sham surgeries (N=7-8/group), and euthanized 8 months post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected timepoints. Pancreatic gene expression and islet morphology were determined at study endpoint. Results: There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG (p=0.06). CBA and OVX decreased expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. Conclusions: CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction, that may be exacerbated by alcohol use and ovarian hormone loss.

SERUM LEPTIN LEVELS AND PANCREATIC ENDOCRINE FUNCTION IN BARIATRIC PATIENTS

Background. Leptin is a hormone synthetized and secreted by the adipose tissue, with a regulating role in the neuro-endocrine-metabolic functions in humans during fasting. Obesity associates metabolic syndrome which combines a leptin resistance status with an insulin resistance status, a disorder that increases the risk of occurrence of type 2 diabetes mellitus. After the bariatric treatment, the decrease of leptin levels in obese patients improves the endocrine function of the pancreas and decreases the risk of developing type 2 diabetes mellitus over time. Aim. In the present study, we have monitored the dynamics of the serum values of leptin, insulin and glucose in correlation with the decrease of BMI (body mass index) after the bariatric surgery. Material and methods. Glucose, insulin and leptin serum levels were assessed in 48 obese individuals before and at 6 months after the bariatric surgery. Results. Leptin and insulin serum levels are decreasing significantly along with the decrease of BMI and pancreatic beta cells optimize their endocrine functionality. Conclusion. Pancreatic endocrine function in obese individuals who undergo bariatric treatment improves significantly at 6 months after the surgery procedure.

Insulin Smart Drug Delivery Nanoparticles of Aminophenylboronic acid–POSS Molecule at Neutral pH

Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3-aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency : 73.2%; loading capacity : 50.5%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 µg/ml POSS-APBA and POSS-APBA@Insulin in HeLa cells and HDF cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.