Decreased Insulin Sensitivity Research Articles

Relationship Between Serum Testosterone, Leptin,Interleukin-6 (il-6) Level and Insulin Sensitivity in Non-obese and Obese Male Subjects in Magway Region, Myanmar

Objective: To determine the relationship between insulin resistance and related variables (serum testosterone, interleukin (IL-6) and leptin level) in obese and non-obese healthy subjects. Methods: Community-based crosssectional, analytic study was undertaken in 60 subjects for each obese group (BMI ≥ 30.0 kg/m2) and non-obese group (BMI 18.5 to 24.9 kg/m2) (age;18-45 years) residing in Magway Township from December 2016 to December 2017. Serum insulin, testosterone, IL-6 and leptin levels were measured by enzyme linked immunoassay, and serum fasting glucose was measured by glucose oxidase method. Insulin sensitivity was calculated by HOMA formula (Homeostatic Model Assessment). Results:HOMA-IR, serum leptin and IL-6 level were significantly higher in obese group while serum testosterone level was significantly lower in obese group. There was a significantly correlation between HOMA-IR with leptin (r=0.306, p=0.001), IL-6 (r=0.237, p=0.009) and testosterone (r=-0.209,p=0.02). Moreover, serum leptin was significantly and positively correlated with IL-6 (r=0.391, p<0.001) while serum testosterone was significantly and negatively correlated with leptin (r=-0.408, p<0.001), and IL-6 (r=-0.34, p<0.001).Conclusions:Obese men are more likely to have low testosterone, high inflammatory markers leptin and Il-6, which were associated with decreased insulin sensitivity.

Microalbuminuria as a potential biomarker for Parkinson’s disease severity: A hypothesis

Parkinson’s disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients’ quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.

Increasing preweaning milk replacer supply affects postweaning energy metabolism of Holstein male calves

Male Holstein calves commonly receive minimal quantities of milk replacer (MR) to speed up weaning and reduce costs. Studies with Holstein female calves show that early life feed restriction affects energy metabolism later in life. Aiming to test this hypothesis, 120 Holstein bull calves (48.4 ± 2.2 kg of BW and 20 ± 3.2 d of age) housed in 24 pens were blocked and randomized to two treatments: A low calf MR allowance (LP) (two daily doses of 2 l each, 582 g/d of DM), or a high MR allowance (HP) (two daily meals of 4 l each, 1164 g/d of DM). Calves were weaned at day 49 of the study and slaughtered at 32.8 ± 0.5 weeks of age. Throughout the study, animals had ad libitum access to a common compound feed, straw, and water. Twenty-four animals were randomly selected for an intravenous glucose tolerance test (IVGTT). The IVGTT was performed at week 6 and 12 of the study and consisted of an intravenous glucose infusion and sequential blood sampling up to 90 min after glucose infusions. Calves were heavier for HP until week 12, after which the difference disappeared. By design, the MR intake was higher in the HP group resulting in a higher energy intake and a higher average daily gain in the preweaning phase. Blood glucose curves were not different at week 6, but at week 12, 5 min after the infusion, glucose was higher in HP calves. Insulin curves were not different at week 6. Nevertheless, in week 12, a higher insulin concentration was observed for HP 5, 10, 15, 20, 30, 35, and 45 min’ postinfusion, indicating a higher requirement of insulin to control glycemia. Differences between HP and LP calves were also observed for the quantitative insulin sensitivity check index, maximum insulin concentration, and insulin delta at week 12. Blood glucose reached maximum concentration within 5–10 min of the IVGTT test, and the concentration was, on average, 8.58 and 10.80 mmol/l at weeks 6 and 12, respectively. Insulin reached maximum concentration within 10–15 min of the IVGTT, and concentrations were, on average, 33.32 and 32.61 μUI/ml at weeks 6 and 12, respectively. Doubling MR supply improved animal growth up to weaning, but these differences disappeared by the end of the feeding period. Despite similar responses to glucose infusions preweaning, higher milk supply seemed to decrease insulin sensitivity after weaning.

PENYULUHAN TENTANG KHASIAT TANAMAN BAU-BAU UNTUK OBAT ANTIDIABETES PADA PUSKESMAS TALUN KENAS

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia associated with abnormal carbohydrate metabolism, fats, and protein caused by decreased insulin secretion or decreased insulin sensitivity, or both and cause chronic microvaskular, and neuropathic complication. Plants are a source of secondary metabolite compounds that are useful as medicine. Many types of plants have activities as traditional medicines, one of which is the odorous plant leaves (chromolaena odorata L.) belonging to the Asteraceae family, traditionally used for wound healing, treating infections, diarrhea, antihypertensive, anti-inflammatory, and diuretic. The odor plant (Chromolaena odorata L.) is reported to contain various compounds in the form of essential oils, flavonoids, alkaloids, phenols, saponins, and tannins.Glibenklamid is a group of sulfonylurea drugs that work to stimulate insulin secretion in the pancreas. Compouds that play a role in reducing blood glucose level in bau-bau leaves is flavonoids, tanin, saponins, alkaloids. This researchaims to evaluate the effect of bau-bau leaves ekstract in reducing the glucose level of wistar strain rats. Test results shown that ethanol bau-bau leaves extract with a dose of 100, 200, 300 mg/kgbb was able to reduce blood glucosse levels in diabetic rats induced by allixan and in the positive control of glibenclamide decreased KGD 105 mg/dL. The conclusion of this reserach was leaves bau-bau extract can reduce blood glucose levels in 300 mg/kgbb is the most effective 77 mg/dL.

A Multisystemic Pictorial Review of Diabetes Mellitus

Diabetes mellitus is a leading cause of death with immense burden on the health care system. The number of patients suffering from diabetes is expected to rise dramatically in the coming years secondary to lifestyle changes. Diabetes is a multisystemic disease that exerts its effects through decreased insulin sensitivity leading to various degrees of metabolic dysregulation. The pathogenesis of complications associated with diabetes is largely dependent on the duration of the disease and common coexisting conditions such as hyperlipidemia, hypertension, and obesity. Acute hyperglycemic and hypoglycemic events can lead to life-threatening illness such as acute coronary syndrome, hyperosmolar state, and diabetic ketoacidosis. The deleterious effects of long-standing diabetes are usually mediated by microvascular disease leading to diabetic retinopathy, nephropathy, cardiomyopathy, and neuropathy.

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.

AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice

Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1.

A study of isolated hyperglycemia (blood glucose ≥155 mg/dL) at 1-hour of oral glucose tolerance test (OGTT) in patients with β-transfusion dependent thalassemia (β-TDT) followed for 12 years.

Objective:Subjects with normal glucose tolerance (NGT) but 1-hour post-load plasma glucose (1-h OGTT) ≥ 155 mg/dl (8.6 mmol/L; H-NGT) have an increased risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk factor category with deeper metabolic impairment. The aim of this study was to evaluate the H-NGT as a diagnostic predictor of future dysglycemia in β-transfusion dependent thalassemia (β-TDT). Indices of insulin secretion and insulin sensitivity derived at baseline from OGTTs, were also reviewed.Study design and methods:OGTT and indices of insulin secretion and insulin sensitivity, derived at baseline during OGTT, in 17 β-TDT with H-NGT and 29 β-TDT with normal OGTT (NGT) and without H-NGT followed for 12 years were studied.Results:H-NGT was associated with decreased insulin sensitivity and progressive deterioration of glucose tolerance. At baseline, serum ferritin and serum alanine aminotransferase (ALT) levels were higher in patients with H-NGT compared to patients with NGT. A strong correlation was observed between ALT and 1-hour plasma glucose value during OGTT in the total group of 36 patients . Compliance to iron chelation therapy was poor in β-TDT patients with H-NGT. An inverse correlation was found between 1-hour plasma glucose value during OGTT and insulin secretion-sensitivity index-2 (ISSI-2) (r: -0.3298; p: 0.025), between ISSI-2 and ALT (r: -0.3262; p: 0.027), and between 1-hour plasma glucose value and ISSI-2 (r: -0.537; p: 0.005) in the whole group of β-TDT patients enrolled in our study.Conclusions:It is of paramount importance to screen early β-TDT patients at increased risk for glucose dysregulation. This retrospective study displayed that finding an isolated high 1-hour post-load glucose level (≥155 mg/dL; H-NGT) during the OGTT may serve as a simple biomarker to detect high-risk patients, with chronic liver disease and/or iron overload, who need periodic glycemic surveillance. Measuring the ISSI 2 represented another valuable predictive marker in the assessment of glycemia in these patients.

Amyotrophic lateral sclerosis (ALS) and the endocrine system: Are there any further ties to be explored?

Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular atrophy, primary lateral sclerosis, and pseudobulbar palsy. Even though endocrine dysfunction independently impacts the ALS-related survival rate, the complex connection between ALS and the endocrine system has not been studied in depth. Here we review earlier and recent findings on how ALS interacts with hormones a) of the hypothalamus and pituitary gland, b) the thyroid gland, c) the pancreas, d) the adipose tissue, e) the parathyroid glands, f) the bones, g) the adrenal glands, and h) the gonads (ovaries and testes). Of note, endocrine issues should always be explored in patients with ALS, especially those with low skeletal muscle and bone mass, vitamin D deficiency, and decreased insulin sensitivity (diabetes mellitus). Because ALS is a progressively deteriorating disease, addressing any potential endocrine co-morbidities in patients with this malady is quite important for decreasing the overall ALS-associated disease burden. Importantly, as this burden is estimated to increase globally in the decades to follow, in part because of an increasingly aging population, it is high time for future multi-center, multi-ethnic studies to assess the link between ALS and the endocrine system in significantly larger patient populations. Last, the psychosocial stress experienced by patients with ALS and its psycho-neuro-endocrinological sequelae, including hypothalamic-pituitaryadrenal dysregulation, should become an area of intensive study in the future.

Role of hormones in sarcopenia.

Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.

Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study.

To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties. A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users. Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly. Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women.

Serum Carboxy Methyl Lysine, Insulin Resistance and Sensitivity in Type 2 Diabetes Mellitus and Diabetic Nephropathy Cases; an Observational Study

Objective: Diabetes Mellitus (DM) and one of its types; type 2 diabetes mellitus (T2DM) is more prevalent from adolescent across the globe, invariable of heredity and age. Diet restriction shall cope up and help body metabolism to absorb the required nutrition and eliminate the junk out of body under healthy diet. Masking of insulin action on target cells leads to insulin resistance (IR) and decreased insulin sensitivity (IS) resulting in increased glycated products such, glycated hemoglobin, glycated albumin and other glycated macromolecules called Advanced Glycation End products. Along with AGE and diabetic profiling, BMI, insulin and lipid profiling may help elucidate the correlation between CML and glucose metabolism in diabetics and diabetic nephropathy cases. CML is formed by Glycoxidation and lipoxidation. Thereby, main objective of this study includes basic renal profiling was also performed to assess kidney functioning and finding its relation with CML. Results: Correlation of CML with important diabetic and metabolic syndrome parameters were performed, giving a supportive evidence for labeling CML as harmful molecule. CML positively correlated with HbA1c, TG and HOMA IR and negatively correlated with QUICKI in group 2 signifying increased damage to tissues due to collective action of glucose, lipid and insulin resistance. Monitoring plasma CML regularly during follow up along with HbA1c may help keep track on plasma glucose status and its deleterious effects on tissues thereby preventing erosion of tissue and vascular lining.

Study of Insulin Resistance in Patients with Cancer

Abstract. The pro-oncogenic effects of obesity, insulin resistance and hyperinsulinemia have been proven in some types of cancer, as well as in type 2 diabetes mellitus.&#x0D; The objective of the research was to investigate the state of insulin resistance in patients suffering from oncological diseases and to compare insulin correlations in patients with type 2 diabetes mellitus and those with cancer.&#x0D; Materials and Methods. The study included the following groups of patients: Group I included healthy individuals (the control group); Group II comprised patients with type 2 diabetes mellitus; Group ІІІ included patients with cancer: subgroup IIIa comprised patients with breast cancer, subgroup IIIb included patients with endometrial cancer, subgroup IIIс comprised patients with colorectal cancer. Fasting blood glucose was determined by glucose oxidase method; hemoglobin A1c was determined by ion exchange chromatography; the levels of insulin and insulin-like growth factor-1 were determined by immune-enzyme method. Insulin resistance was assessed by the homeostatic model assessment for insulin resistance index. The results obtained were analyzed using statistical analysis.&#x0D; Results. Obesity was confirmed in all the groups of patients with cancer. Significantly higher body mass index, as compared to the control group, was found in patients with endometrial cancer (p = 0.008). In comparison with the control group, the levels of insulin and insulin-like growth factor-1 increased significantly in all groups of patients with cancer (p &lt; 0.001). Fasting blood sugar levels and hemoglobin A1c did not differ from the indicators in the control group (p &gt; 0.05). Direct correlations between insulin and body mass index (p &lt; 0.05), insulin-like growth factor-1 (p &lt; 0.05) and the homeostatic model assessment for insulin resistance index in patients of Group II and Group III were detected (p &lt; 0.05).&#x0D; Conclusions. In obese patients with breast, uterine and colorectal cancer, there was found a decrease in insulin sensitivity, which might increase the proliferative effects of insulin and insulin-like growth factor-1. Correlation analysis showed a probable association of cancer and diabetes mellitus due to obesity and insulin resistance.

Predictive network modeling in human induced pluripotent stem cells identifies key driver genes for insulin responsiveness.

Insulin resistance (IR) precedes the development of type 2 diabetes (T2D) and increases cardiovascular disease risk. Although genome wide association studies (GWAS) have uncovered new loci associated with T2D, their contribution to explain the mechanisms leading to decreased insulin sensitivity has been very limited. Thus, new approaches are necessary to explore the genetic architecture of insulin resistance. To that end, we generated an iPSC library across the spectrum of insulin sensitivity in humans. RNA-seq based analysis of 310 induced pluripotent stem cell (iPSC) clones derived from 100 individuals allowed us to identify differentially expressed genes between insulin resistant and sensitive iPSC lines. Analysis of the co-expression architecture uncovered several insulin sensitivity-relevant gene sub-networks, and predictive network modeling identified a set of key driver genes that regulate these co-expression modules. Functional validation in human adipocytes and skeletal muscle cells (SKMCs) confirmed the relevance of the key driver candidate genes for insulin responsiveness.

Disorders of microcirculation in a comorbid patient

Background. Diabetes mellitus (DM) is a global epidemic. According to the experts, by 2045 the number of patients with diabetes will rise by 48 %. Patients with diabetes are characterized by the high cardiovascular mortality and a significant reduction in life expectancy. Almost half of the deaths associated with diabetes are due to cardiovascular diseases (CVD). Patients with diabetes often have concomitant pathology (hypertension, dyslipidemia, obesity), which increases the cardiovascular risk.&#x0D; Objective. To describe microcirculation disorders in patients with comorbid conditions.&#x0D; Materials and methods. Analysis of literature sources on this topic.&#x0D; Results and discussion. Type 2 diabetes (DM2) is a multifaceted disease that has a number of cardiovascular, metabolic and renal complications. The links of the pathogenesis of cardiovascular complications of DM2 include dyslipidemia, systemic inflammation, insulin resistance, autonomic imbalance, and endothelial dysfunction (ED). ED leads to vasoconstriction, increased chronic inflammation, increased vascular permeability and hypercoagulation, which ultimately causes micro- and macroangiopathy. Neurological complications of diabetes are also mediated by ED and microangiopathies, which lead to nerve hypoxia with a decrease in conductivity velocity. In recent years, the literature has been actively discussing the syndrome of early vascular aging – premature and accelerated development of structural and functional age-related changes in blood vessels. Microcirculation disorders that accompany diabetes, CVD and their complications are mediated by nitric oxide (NO) imbalance. NO reduces the contractility and proliferation of smooth muscle cells, platelet aggregation, endothelin production, adhesion of monocytes and platelets, and oxidation of low-density lipoproteins. In humans, NO is produced from L-arginine. Increased L-arginase activity and decreased NO-synthase activity lead to a decrease in NO content and to the development of ED, atherosclerosis, and decreased insulin sensitivity. L-arginine as a substrate of NO improves the functional state of the endothelium, reduces the manifestations of oxidative stress, reduces the level of pro-inflammatory cytokines and adhesion molecules, inhibits platelet aggregation, reduces insulin resistance. It should be noted that the administration of 4.2 g of L-arginine in DM is not enough. In clinical studies, doses of 6.4-9 g per day were found to be effective in diabetes and obesity. Therefore, it is advisable to use Tivortin-200 (“Yuria-Pharm”), which contains 8.4 g of L-arginine in one vial.&#x0D; Conclusions. 1. Patients with diabetes are characterized by the high cardiovascular mortality and a significant reduction in life expectancy. 2. The links of the pathogenesis of cardiovascular complications of DM2 include dyslipidemia, systemic inflammation, insulin resistance, autonomic imbalance, and ED. 3. Disorders of microcirculation that accompany diabetes, CVD and their complications, are mediated by NO imbalance. 4. L-arginine as a substrate of NO improves the functional state of the endothelium, reduces the manifestations of oxidative stress, reduces the level of pro-inflammatory cytokines and adhesion molecules, inhibits platelet aggregation, reduces insulin resistance. 5. In diabetes and obesity, it is advisable to use Tivortin-200, which contains 8.4 g of L-arginine in one vial.

Chronic prepartum light-dark phase shifts in cattle disrupt circadian clocks, decrease insulin sensitivity and mammary development, and are associated with lower milk yield through 60 days postpartum

Circadian and metabolic systems are interlocked and reciprocally regulated. To determine if the circadian system regulates glucose homeostasis and mammary development, the function of the circadian system was disrupted by exposing cattle to chronic light-dark cycle phase shifts from 5 wk before expected calving (BEC) to parturition. Multiparous Holstein cows were exposed to 16 h of light and 8 h of dark (CON, n = 8) or phase shifting (PS, n = 8) the light cycle 6 h every 3 d beginning 35 d BEC. After calving, both treatments were exposed to CON lighting. Mammary biopsies were taken at 21 d BEC and 21 d in milk (DIM), and histological analysis indicated PS treatment decreased the ratio of lumen to alveolar area and percentage of proliferating epithelial cells in the prepartum period. Intravenous glucose tolerance test was performed at 14 d BEC and 7 DIM by administering 50% dextrose. Blood glucose, β-hydroxybutyrate, insulin, and nonesterified fatty acids were consequently measured over 3 h. At 14 d BEC no treatment differences were observed in baseline glucose or insulin. Treatment had no effect on blood glucose or glucose area under the curve at 14 d BEC and 7 DIM. Insulin area under the curve was higher in PS versus CON at 14 d BEC and 7 DIM. The PS cows produced less milk than CON cows through 60 DIM (40.3 vs. 42.6 kg/d). Exposure to chronic light-dark PS in late gestation decreased mammary development and increased insulin resistance in periparturient cows, which may have caused subsequent lower milk yield.

Adipocyte-specific deletion of zinc finger protein 407 results in lipodystrophy and insulin resistance in mice

PPARγ deficiency in humans and model organisms impairs the transcriptional control of adipogenesis and mature adipocyte function resulting in lipodystrophy and insulin resistance. Zinc finger protein 407 (ZFP407) positively regulates PPARγ target gene expression and insulin-stimulated glucose uptake in cultured adipocytes. The in vivo physiological role of ZFP407 in mature adipocytes, however, remains to be elucidated. Here we generated adipocyte-specific ZFP407 knockout (AZKO) mice and discovered a partial lipodystrophic phenotype with reduced fat mass, hypertrophic adipocytes in inguinal and brown adipose tissue, and reduced adipogenic gene expression. The lipodystrophy was further exacerbated in AZKO mice fed a high-fat diet. Glucose and insulin tolerance tests revealed decreased insulin sensitivity in AZKO mice compared to control littermates. Cell-based assays demonstrated that ZFP407 is also required for adipogenesis, which may also contribute to the lipodystrophic phenotype. These results demonstrate an essential in vivo role of ZFP407 in brown and white adipose tissue formation and organismal insulin sensitivity.

Bone and insulin resistance - a literature review

Insulin resistance (IR) is defined as a decreased tissue response to insulin-mediated cellular activity. Decreased insulin sensitivity and concomitant hyperinsulinemia are known to play a central role in metabolic disorders associated with obesity, metabolic syndrome (MetS) and type 2 diabetes mellitus (DM). In recent years, more and more research has been focused on the relationship between IR and bone health. In vitro, physiological concentrations of insulin have been shown to increase osteoblast proliferation rate, collagen synthesis, alkaline phosphatase production, and glucose uptake and to inhibit osteoclast activity. This evidence indicates that insulin acts as an anabolic agent on bone. It remains to be discussed whether osteoblasts retain their sensitivity to insulin in states of IR. On the one hand, a large number of clinical studies have established that IR and concomitant hyperinsulinemia are positively associated with bone mineral density (BMD), both in individuals with or without overt DM. On the other hand, a number of researchers have found suppressed bone metabolism and decreased bone volume in an IR state . The data on the effect of IR on bone microarchitectonics and bone strength are also controversial. In relation to these data, it remains unclear whether the net effect of IR is favorable or unfavorable for bone health and fracture risk.

Association of depressive disorder with the cognitive performance of Mexican older adults with type 2 diabetes mellitus

AbstractBackgroundType 2 diabetes mellitus (T2D) and depression have both become pandemics over the last years. Both of these conditions have also been associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction, all identified as risk factors for cognitive impairment and dementia. Our aim in this study was to explore the effect of depressive symptoms in the cognitive performance of Mexican older adults diagnosed with with T2D.MethodWe analyzed differences in global cognition (using the COGSCORE instrument) of adults aged 65 and over, with T2D, with a three‐year follow up within the 10/66 Dementia Research Group protocols in Mexico. T2D was diagnosed with glucose levels at baseline equal or greater than 126 mg/dl, and/or with self‐report of diabetes. Depression diagnosis was based on the International Classification of Diseases glossary version 10 (ICD‐10).ResultsThe total sample consisted of 441 older adults people with T2D. 65% were women. The majority (72%) were outside glycemic control levels, 45% were overweight and 27% were depressed. In termos of cognitive performance, there was no significant difference in subjects with diabetes and depressive symptoms (p&gt;0.47). When comparing the cognitive performance, there were differences between 1) the ages of 75 and 79 (p&lt;0.052) and 80 or more (p&lt;0.013) with the group of 65‐69 years; and 2) between those with low or normal BMI compared to those with obesity (p&gt;0.56). Variables such as depression, area of study, educational level, marital status, and mass index showed no statistical significance.ConclusionIn this study, we found that in a Mexican population with T2D the presence of depression did not show a significant effect on cognitive performance, which is controversial with other studies. Interestingly, those who were underweight or had a normal BMI had a decrease in cognitive function, so we must pay attention to mental health but also complement it with nutrition and establish prioritary intervention measures that allow weight control, decrease chronic degenerative diseases, and that could consequently reduce cognitive impairment.

Four sesquiterpene glycosides from loquat (Eriobotrya japonica) leaf ameliorates palmitic acid-induced insulin resistance and lipid accumulation in HepG2 Cells via AMPK signaling pathway.

Insulin resistance (IR), caused by impaired insulin signal and decreased insulin sensitivity, is generally responsible for the pathophysiology of type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides (SGs), the exclusive natural products from loquat leaf, have been regarded as potential lead compounds owing to their high efficacy in hypoglycemia and hypolipidemia. Here, we evaluated the beneficial effects of four single SGs isolated from loquat leaf, including SG1, SG2, SG3 and one novel compound SG4 against palmitic acid-induced insulin resistance in HepG2 cells. SG1, SG3 and SG4 could significantly enhance glucose uptake of insulin-resistant HepG2 cells at non-cytotoxic concentration. Meanwhile, Oil Red O staining showed the decrease of both total cholesterol and triglyceride content, suggesting the amelioration of lipid accumulation by SGs in insulin-resistant HepG2 cells. Further investigations found that the expression levels of phosphorylated AMPK, ACC, IRS-1, and Akt were significantly up-regulated after SGs treatment, on the contrary, the expression levels of SREBP-1 and FAS were significantly down-regulated. Notably, AMPK inhibitor Compound C (CC) blocked the regulative effects, while AMPK activator AICAR mimicked the effects of SGs in PA-treated insulin-resistant HepG2 cells. In conclusion, SGs (SG4>SG1≈SG3>SG2) improved lipid accumulation in insulin-resistant HepG2 cells through the AMPK signaling pathway.