BackgroundOrganophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process.ResultsHere we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes.ConclusionCollectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1134-6) contains supplementary material, which is available to authorized users.

Background:Thyroid disorders are common in India but scarce data exists on its prevalence in young women.Materials and Methods:This study was conducted in female college students in seven colleges in Madurai District, Tamil Nadu. Thyroid-stimulating hormone (TSH) was used as the screening test to diagnose thyroid dysfunction. The abnormal TSH values were classified as mild TSH elevation (TSH 4.5–10 mIU/ml), significant TSH elevation (TSH > 10 mIU/ml), and low TSH (TSH < 0.4 mIU/ml).Results:A total of 1292 subjects were screened of whom 161 subjects (12.5%) had abnormal TSH. The overall prevalence of elevated TSH was 11% out of which 9.7% had mild TSH elevation. A low TSH was seen in 1.3% of the study population.Conclusion:Thyroid dysfunction was common in young women in south India. One out of every eight young women had thyroid dysfunction, and mild TSH elevation was the most common abnormality.

Background and Objectives:Short stature (SS) is a common pediatric problem and it might be the first sign of underlying illness. Studies documenting the burden and etiological profile of SS are scarce from India and are mostly limited to data obtained from referral centers. Due to the lack of large-scale, community-based studies utilizing a standard protocol, the present study aimed to assess the prevalence and etiological profile of SS in school children of a South Indian district.Materials and Methods:In this cross-sectional study, children aged 4–16 years from 23 schools in Madurai district, Tamil Nadu, underwent anthropometric measurements and height was plotted in Khadilkar et al. growth chart. The cause of SS was assessed using clinical and laboratory evaluations in assigned children with a height less than third centile.Results:A total of 15644 children belonging to 23 schools were evaluated, and 448 (2.86%) children had SS. Etiological evaluation was further performed in 87 randomly assigned children, and it is identified that familial SS or constitutional delay in growth was the most common cause of SS in the study population (66.67%). Hypothyroidism and growth hormone deficiency were the two most common pathological causes of SS seen in 12 (13.79%) and 8 (9.20%) children, respectively. Malnutrition was the cause of SS in 6 (6.9%) children and cardiac disorders, psychogenic SS, and skeletal dysplasia were other identified causes of SS in the study.Interpretation and Conclusions:The overall prevalence of SS in school children was 2.86% and familial SS or constitutional delay in growth was the most common cause of SS. As a significant percentage of children with SS had correctable causes, monitoring growth with a standard growth chart should be mandatory in all schools.

Background Pancreatic acinar cells are commonly co-transplanted along with islets during auto-and allo-transplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and function with supplementation of alpha-1 antitrypsin (A1AT). Methods Acinar cell protease activity, insulin levels, and percent islet loss were measured after culture of pure and impure clinical islet preparations. The effect of proteases on ultra-structure of islets and beta cell insulin granules were examined by transmission electron microscopy (TEM). The number of insulin granules and insulin-labeled immune-gold particles were counted. The in vivo effect of proteases on islet function was studied by transplanting acinar cells adjacent to islet grafts in diabetic mice. The effects of A1AT culture supplementation on protease activity, insulin levels, and islet function were assessed in pure and impure islets. Results Islet loss after culture was significantly higher in impure relative to pure preparations (30 vs. 14%, p<0.04). Lower islet purity was associated with increased protease activity and decreased insulin levels in culture supernatants. Reduced beta cell insulin granules and insulin degradation by proteases were confirmed by TEM. Transplantation results showed delayed islet graft function when acinar cells were transplanted adjacent to the islets under the kidney capsule. Supplementation of A1AT to impure islet cultures maintained islet mass, restored insulin levels, and preserved islet functional integrity. Conclusions Culture of impure islets in the presence of A1AT prevents insulin degradation and improves islet recovery.

While it is known that islet cell mass increases considerably after birth, general uncertainty surrounds the source of new beta cells in humans. Chronic pancreatitis (CP) presents a natural injury model for studying postnatal beta-cell regeneration in the human pancreas. In this report, we present histological evidence from human CP pancreases to support the theory that islet neogenesis can occur from ductal precursor cells after birth. Three young patients (ages 16, 12, and 28 years) underwent total pancreatectomy for the management of CP followed by islet isolation and autologous transplantation to prevent or minimize post-surgical diabetes. In all cases, the pancreases had extensive fibrosis, a rock-like consistency, and calcifications in the ducts. During islet isolations, we observed the unusual release of islets with many ductal fragments. In histopathological evaluation of these pancreases, solid cords of cells sometimes formed islet like structures intraductally or extending from ductal structures. Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both β-cells and α-cells. Labeling for Ki67 to demonstrate mitotic activity showed frequent labeling of duct epithelial cells and of some periductal cells. Using insulin and wide-spectrum cytokeratin double-immunofluorescent labeling, we found insulin positive cells to be present within the ductal lumens, among the cytokeratin positive ductal epithelium, and extending from the ductal epithelium into surrounding connective tissues, providing evidence for a ductal origin of islet neogenesis.