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2023 SEP 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators publish new report on proinsulin. According to news reporting originating from [...]

Background: Insulin resistance (IR) and liver steatosis (LS) are interlinked metabolic derangements whose prevalence is rapidly increasing, but the effect of dietary carbohydrate quality on LS is unknown. Objective: The objective was to describe the relation of IR and LS to total carbohydrate, total dietary fiber, and the glycemic index (GI) and glycemic load of the diet. Design: The study was a cross-sectional evaluation of 247 apparently healthy subjects who had no evidence of viral, toxic, or autoimmune hepatitis and who were unselected for alcohol intake. The homeostasis model assessment index was used as a surrogate measure of IR, and a liver echography was used as a proxy for LS grading. Dietary data were collected by using 3-d food records. Total carbohydrate intake, total dietary fiber, GI, and glycemic load were calculated by using a semiquantitative food-frequency questionnaire concerning the dietary sources of carbohydrates. Results: The prevalence of high-grade LS (HG-LS) increased significantly across quartiles of dietary GI (P for trend < 0.034): HG-LS in the 4th quartile (high GI) was twice that in the first 3 quartiles (low to medium GIs), whereas no relation was observed with total carbohydrates, total dietary fiber, or glycemic load. In insulin-sensitive subjects (first 3 quartiles of homeostasis model assessment index of IR), the prevalence of HG-LS did not differ significantly between GI groups, but, in insulin-resistant subjects (4th quartile of homeostasis model assessment index of IR), it was twice as high in those with high GI as in those with low to medium GIs (P = 0.005). Conclusions: High-GI dietary habits are associated with HG-LS, particularly in insulin-resistant subjects. Dietary advice on the quality of carbohydrate sources therefore may be a complementary tool for preventing or treating LS of metabolic origin. Am J Clin Nutr 2006;84:136-42. KEY WORDS Diet, glycemic index, insulin resistance, liver steatosis, metabolic syndrome

Phosphatidylinositol (PI) 4,5-bisphosphate (PI[P.sub.2]) plays a pivotal role in insulin-stimulated glucose transport as an important precursor to PI 3,4,5-trisphosphate (PI[P.sub.3]) and a key regulator of actin polymerization. Since endothelin (ET)-1 impairs insulin sensitivity and PI[P.sub.2] is a target of ET-1-induced signaling, we tested whether a change in insulin-stimulated PIPS generation and signaling, PI[P.sub.2]-regulated actin polymerization, or a combination of both accounted for ET-1-induced insulin resistance. Concomitant with a time-dependent loss of insulin sensitivity, ET-1 caused a parallel reduction in plasma membrane PI[P.sub.2]. Despite decreased insulin-stimulated PI 3-kinase activity and PI[P.sub.3] generation, ET-1 did not diminish downstream signaling to Akt-2. Furthermore, addition of exogenous PI[P.sub.2], but not PI[P.sub.3], restored insulin-regulated GLUT4 translocation and glucose transport impaired by ET-1. Microscopic and biochemical analyses revealed a PI[P.sub.2]-dependent loss of cortical filamentous actin (F-actin) in ET-1-treated cells. Restoration of insulin sensitivity by PI[P.sub.2] add-back occurred concomitant with a reestablishment of cortical F-actin. The corrective effect of exogenous PI[P.sub.2] in ET-1-induced insulin-resistant cells was not present in cells where cortical F-actin remained experimentally depolymerized. These data suggest that ET-1-induced insulin resistance results from reversible changes in PI[P.sub.2]-regulated actin polymerization and not PI[P.sub.2]-dependent signaling., In muscle and adipose tissues, insulin stimulates glucose transport by increasing the level of the glucose transporter protein GLUT4 (1) at the plasma membrane (1,2). Extensive study demonstrates that insulin [...]

Epidemiological evidence suggests that sex differences exist in type 2 diabetes. Men seem to be more susceptible than women to the consequences of obesity and sedentary lifestyle, possibly because of differences in insulin sensitivity and regional body fat deposition. Thus, lacking androgen receptor (AR) in male individuals may promote insulin resistance. To determine whether lacking AR in male individuals contributes to in vivo insulin resistance, an AR knockout model (A[R.sup.-/y]) was used to study the correlation between AR and insulin resistance. Progressive reduced insulin sensitivity and impaired glucose tolerance were seen in (A[R.sup.-/y]) mice with advancing age. Aging (A[R.sup.-/y]) mice displayed accelerated weight gain, hyperinsulinemia, and hyperglycemia, and loss of AR contributes to increased trigiyceride content in skeletal muscle and liver. Leptin is higher in serum of (A[R.sup.-/y]) mice. Treatment with exogenous leptin fails to stimulate weight loss in (A[R.sup.-/y]) mice in advanced age, suggesting leptin resistance in the (A[R.sup.-/y]) mice. Exogenous dihydrotestosterone replacement fails to reverse the metabolic abnormalities and insulin resistance in (A[R.sup.-/y]) mice. Our in vivo studies demonstrate that androgen-AR plays key roles in the development of insulin and leptin resistance, which may contribute to the development of type 2 diabetes and cardiovascular disease., It is estimated that by the year 2030, there will be ~366 million people affected by type 2 diabetes worldwide (1), with many of those affected in the elderly age [...]

OBJECTIVE--Several studies have shown a bimodal curve in the distribution of glucose in populations with a high prevalence of type 2 diabetes, but bimodality has not been reported among whites [...]

OBJECTIVE--Insulin resistance is associated with autonomic dysfunction. An attenuated decrease in heart rate a tier exercise (or heart rate recovery [HRR]) predicts all-cause mortality and is believed to reflect decreased [...]

OBJECTIVE--In later stages of type 2 diabetes, proinsulin and proinsulin-like molecules are secreted in increasing amounts with insulin. A recently introduced chemiluminescence assay is able to detect the uncleaved 'intact' [...]

Nonautoimmune ketosis-prone diabetic syndromes are increasingly frequent in nonwhite populations. We have characterized a cohort of patients of sub-Saharan African origin who had ketosis-prone type 2 diabetes (n = 111), type 1 diabetes (n = 21), and type 2 diabetes (n = 88) and were admitted to a hospital for management of uncontrolled diabetes. We compared epidemiological, clinical, and metabolic features at diabetes onset and measured insulin secretion (glucagon-stimulated C-peptide) and insulin action (short intravenous insulin tolerance test) during a 10-year follow-up. Ketosis-prone type 2 diabetes shows a strong male predominance, stronger family history, higher age and BMI, and more severe metabolic decompensation than type 1 diabetes. In ketosis-prone type 2 diabetes, discontinuation of insulin therapy with development of remission of insulin dependence is achieved in 76% of patients (non-insulin dependent), whereas only 24% of patients remain insulin dependent. During evolution, ketosis-prone type 2 diabetes exhibit specific β-cell dysfunction features that distinguish it from type 1 and type 2 diabetes. The clinical course of non-insulin-dependent ketosis-prone type 2 diabetes is characterized by ketotic relapses followed or not by a new remission. Progressive hyperglycemia precedes and is a strong risk factor for ketotic relapses (hazard ratio 38). The probability for non-insulin-dependent ketosis-prone type 2 diabetes to relapse is 90% within 10 years, of whom ~50% will become definitively insulin dependent. Insulin sensitivity is decreased in equal proportion in both ketosis-prone type 2 diabetes and type 2 diabetes, but improves significantly in non-insulin-dependent ketosis-prone type 2 diabetes, only after correction of hyperglycemia. In conclusion, ketosis-prone type 2 diabetes can be distinguished from type 1 diabetes and classical type 2 diabetes by specific features of clinical pathophysiology and also by the natural history of β-cell dysfunction and insulin resistance reflecting a propensity to glucose toxicity., The pathogenesis of diabetes distinguishes type 2 diabetes, resulting from the interaction between insulin resistance and β-cell dysfunction (1), from type 1 diabetes, in which the autoimmune destruction of pancreatic [...]

Insulin resistance and obesity are both associated with lower plasma adiponectin concentrations. Since insulin resistance and obesity are related, the extent to which the association of adiponectin with insulin resistance is dependent on its relationship with obesity is unclear. To address this issue, fasting plasma adiponectin concentrations were measured in 60 nondiabetic subjects, stratified into four equal groups on the basis of both their degree of adiposity and insulin resistance. Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration in response to an infusion of octreotide, glucose, and insulin, and degree of adiposity was assessed by BMI. Subjects were defined as obese (BMI ≥ 30.0 kg/[km.sup.2]) or nonobese ( 190 mg/dl). Insulin-resistant subjects had significantly (P < 0.001) lower (mean ± SD) adiponectin concentrations, whether they were obese (17.1 ± 5.9 µg/ml) or nonobese (16.3 ± 7.5 µg/ml) as compared with either obese, insulin-sensitive (34.3 ± 13.1 µg/ml) or nonobese, insulin-sensitive (29.8 ± 15.3 µg/ml) subjects. Finally, adiponectin levels in insulin-sensitive subjects varied to a significantly greater degree than in insulin-resistant subjects. These results suggest that adiponectin concentrations are more closely related to differences in insulin-mediated glucose disposal than obesity., An association between and insulin adipokines resistance has been noted in both diabetic and nondiabetic states (1-3). Of particular interest have been the recent demonstrations that adiponectin may play a [...]

The aim of the present study was to determine the specific sites of impairment to muscle glucose uptake (MGU) in the insulin-resistant high-fat-fed, conscious C57BL/6J mouse. Wild type (WT) and hexokinase II overexpressing (H[K.sup.Tg]) mice were fed either a standard diet or high-fat diet and studied at 4 months of age. A carotid artery and jugular veins had catheters chronically implanted for sampling and infusions, respectively, and mice were allowed to recovery for at least 5 days. Mice were fasted for 5 h and underwent a hyperinsulinemic-euglycemic clamp or saline infusion for 120 min. Separate groups of mice were studied during 30-min sedentary or treadmill exercise periods. A bolus of 2-deoxy[³H]glucose was administered 25 min before the end of each study for determination of [R.sub.g], an index of tissue-specific glucose uptake. Fasting blood glucose was increased in high-fat compared with standard diet-fed WT (194 ± 4 vs. 171 ± 4 mg/dl) but not H[K.sup.Tg] (179 ± 5 vs. 171 ± 3 mg/dl) mice. High-fat feeding created hyperinsulinemia in both WT and H[K.sup.Tg] mice (58 ± 8 and 77 ± 15 µU/ml) compared with standard diet-fed mice (21 ± 2 and 20 ±1 µU/ml). [R.sub.g] was not affected by genotype or diet during either saline infusion or sedentary conditions. HK II overexpression augmented insulin-stimulated [R.sub.g] in standard diet-fed but not high-fat-fed mice. Exercise-stimulated [R.sub.g] was impaired by high-fat feeding in WT mice, but this impairment was largely rectified in H[K.sup.Tg] mice. In conclusion, high-fat feeding impairs both insulin- and exercise-stimulated MGU, but only exercise-stimulated MGU was corrected by HK II overexpression., Insulin resistance induced by high-fat feeding is characterized by a decrease in insulin-stimulated glucose disposal (1-3). The impaired glucose disposal is likely to be due to deficits in one or [...]

A 45-year old soldier presented with headache, polyuria and excessive weight gain for many weeks. He also noticed increase in shoe size, tightening of ring around his finger and coarsening of facial features with widening of nose and thickening of lips for last one year. He also complained of backache, electric shock like sensation in gloves and stocking distribution as well as excessive sweating and darkening of her skin in flexural areas. Examination revealed a large framed man with coarse facial features, large hands and feet, acanthosis nigricans and many skin tags. His past medical history was most significant for bilateral carpal tunnel syndrome requiring surgery in last 2 years and type 2 diabetes mellitus which recently was not even controlled on high doses of insulin. His serum insulin like growth factor 1 (IGF-1) and dynamic growth testing was normal. His MRI of pituitary fossa showed no mass while he had normal pituitary hormonal workup. He had marked elevation of fasting serum insulin, and mixed hyperlipidemia. His calculated insulin resistance based on HOMA-IR was very high. Based on negative MRI and clinical and biochemical features of insulin resistance a diagnosis of pseudoacromegaly was made. Pseudoacromegaly is a rare phenomenon that occurs in severe insulin resistance with acromegaloid phenotype in absence of raised growth hormone or IGF-1. Physicians should keep this possibility in mind while evaluating patients with similar clinical and radiological features. Keywords: Pseudoacromegaly | acromegaly | insulin resistance, Case A 45-year old soldier presented to emergency room with headache and polyuria for last many weeks. He also gives history of increase in shoe size from 43 to 46 [...]

The recent report of the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (1) identified as cardiovascular disease (CVD) risk factors what they referred to as a [...]

Metabolically obese, normal-weight (MONW) subjects (BMI Several studies have reported the association of oxidative stress with insulin resistance and hyperinsulinemia in obese subjects (5,6). However, the degree of oxidative stress [...]

ANTIBODIES to the insulin receptor have been described in several diseases including diabetes mellitus with acanthosis nigricans,' Hashimoto's thyroiditis, 2 primary biliary cirrhosis,3 progressive systemic sclerosis,4 Sjbgren's syndrome and systemic [...]