Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.

. Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle.

No abstract

AIMS/HYPOTHESIS: We tested the hypothesis that silent coeliac disease is more frequent than expected in both patients with Type I (insulin-dependent) diabetes mellitus and their first-degree relatives. We evaluated how the presence of other autoimmune disorders in diabetic patients and their first-degree relatives is related to silent, unrecognized coeliac disease. METHODS: Sera from 491 subjects with Type I diabetes, 824 relatives and 4,000 healthy control subjects were screened for anti-endomysial antibodies and all those subjects who tested positive for anti-endomysial antibodies underwent intestinal biopsy. RESULTS: We found that the prevalence of coeliac disease was 5.7 \% among the diabetic patients and 1.9 \% among the relatives, values significantly higher than those found among the control subjects (p < 0.0001; p < 0.001). The prevalence of autoimmune disorders in diabetic patients with coeliac disease was significantly higher than in subjects with Type I diabetes alone (p < 0.0001). The prevalence of autoimmune disorders in the relatives with coeliac disease was significantly higher than in those who tested negative for anti-endomysial antibodies (p = 0.01). CONCLUSION/INTERPRETATION: This report provides further confirmation of the high prevalence of undiagnosed coeliac disease among diabetic patients and their relatives. This interesting new finding is the increased presence of other autoimmune diseases in these patients, as well as in their relatives with a delayed diagnosis for coeliac disease. Patients newly diagnosed with coeliac disease showed excellent compliance with the gluten-free diet. This should encourage policymakers to consider introducing an easy-to-use screening programme for diabetic patients and their relatives into everyday clinical practice, in order to prevent coeliac-associated symptoms and the onset of additional, more serious auto-immune disorders

Aims/hypothesis Insulin effects reportedly involve reactive oxygen species (ROS) and oxidative stress in vitro, but skeletal muscle oxidative stress is an emerging negative regulator of insulin action following high-fat feeding. NEFA may enhance oxidative stress and insulin resistance. We investigated the acute impact of insulin with or without NEFA elevation on muscle ROS generation and insulin signalling, and the potential association with altered muscle mitochondrial function. Methods We used hyperinsulinaemic-euglycaemic clamping, 150 min, without or with lipid infusion to modulate plasma NEFA concentration in lean rats. Results Insulin and glucose (Ins) infusion selectively enhanced xanthine oxidase-dependent muscle ROS generation. Ins with lipid infusion (Ins+NEFA) lowered whole-body glucose disposal and muscle insulin signalling, and these effects were associated with high muscle mitochondrial ROS generation and activation of the proinflammatory nuclear factor-κB inhibitor (IκB)-nuclear factor-κB (NFκB) pathway. Antioxidant infusion prevented NEFA-induced systemic insulin resistance and changes in muscle mitochondrial ROS generation, IκB-NFκB pathway and insulin signalling. Changes in insulin sensitivity and signalling were independent of changes in mitochondrial enzyme activity and ATP production, which, in turn, were not impaired by changes in ROS generation under any condition. Conclusions/interpretation Acute muscle insulin effects include enhanced ROS generation through xanthine oxidase. Additional NEFA elevation enhances mitochondrial ROS generation, activates IκB-NFκB and reduces insulin signalling. These alterations are not associated with acute reductions in mitochondrial enzyme activity and ATP production, and are reversed by antioxidant infusion. Thus, NEFA acutely cause systemic and muscle insulin resistance by enhancing muscle oxidative stress through mitochondrial ROS generation and IκB-NFκB activation.