Disruption Of Glucose Metabolism Research Articles

Rosiglitazone Mitigates Dexamethasone-Induced Depression in Mice via Modulating Brain Glucose Metabolism and AMPK/mTOR Signaling Pathway

Major depressive disorder (MDD) is a common, complex disease with poorly understood pathogenesis. Disruption of glucose metabolism is implicated in the pathogenesis of depression. AMP-activated protein kinase (AMPK) has been shown to regulate the activity of several kinases, including pAKT, p38MAPK, and mTOR, which are important signaling pathways in the treatment of depression. This study tested the hypothesis that rosiglitazone (RGZ) has an antidepressant impact on dexamethasone (DEXA)-induced depression by analyzing the function of the pAKT/p38MAPK/mTOR pathway and NGF through regulation of AMPK. MDD-like pathology was induced by subcutaneous administration of DEXA (20 mg/kg) for 21 days in all groups except in the normal control group, which received saline. To investigate the possible mechanism of RGZ, the protein expression of pAMPK, pAKT, p38MAPK, and 4EBP1 as well as the levels of hexokinase, pyruvate kinase, and NGF were assessed in prefrontal cortex and hippocampal samples. The activities of pAMPK and NGF increased after treatment with RGZ. The administration of RGZ also decreased the activity of mTOR as well as downregulating the downstream signaling pathways pAKT, p38MAPK, and 4EBP1. Here, we show that RGZ exerts a potent inhibitory effect on the pAKT/p38MAPK/mTOR/4EBP1 pathway and causes activation of NGF in brain cells. This study has provided sufficient evidence of the potential for RGZ to ameliorate DEXA-induced depression. A new insight has been introduced into the critical role of NGF activation in brain cells in depression. These results suggest that RGZ is a promising antidepressant for the treatment of MDD.

Triphenyl phosphate proved more potent than its metabolite diphenyl phosphate in inducing hepatic insulin resistance through endoplasmic reticulum stress

Triphenyl phosphate (TPHP) is a widely used flame retardant and plasticizer and has been detected extensively in environmental media, wildlife and human bodies. Several epidemiological and animal studies have revealed that TPHP exposure is positively associated with glucose homeostasis disruption and diabetes. However, the effects of TPHP on hepatic glucose homeostasis and the underlying mechanisms remain unclear. The present work aimed to investigate the cytotoxicity and glucose metabolism disruption of TPHP and its metabolite diphenyl phosphate (DPHP) within hepatocytes. The cell viability assay undertaken on human normal liver (L02) cells showed that TPHP exhibited more potent hepatotoxicity than DPHP. RNA sequencing (RNA-seq) data showed that TPHP and DPHP presented different modes of toxic action. Insulin resistance is one of the predominant toxicities for TPHP, but not for DPHP. The insulin-stimulated glucose uptake and glycogen synthesis were impaired by TPHP, while DPHP exhibited no significant impairment on these factors. TPHP exposure induced endoplasmic reticulum (ER) stress, and the ER stress antagonist 4-PBA restored the impairment of insulin-stimulated glucose uptake and glycogen synthesis induced by TPHP. TPHP could also induce liver ER stress and insulin resistance in mice. Taken together, the results suggested that TPHP induces more potent insulin resistance through ER stress than its metabolite DPHP.

Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants-A Review.

Obesogenic endocrine-disrupting chemicals (EDCs) belong to the group of environmental contaminants, which can adversely affect human health. A growing body of evidence supports that chronic exposure to EDCs can contribute to a rapid increase in obesity among adults and children, especially in wealthy industrialized countries with a high production of widely used industrial chemicals such as plasticizers (bisphenols and phthalates), parabens, flame retardants, and pesticides. The main source of human exposure to obesogenic EDCs is through diet, particularly with the consumption of contaminated food such as meat, fish, fruit, vegetables, milk, and dairy products. EDCs can promote obesity by stimulating adipo- and lipogenesis of target cells such as adipocytes and hepatocytes, disrupting glucose metabolism and insulin secretion, and impacting hormonal appetite/satiety regulation. In vitro models still play an essential role in investigating potential environmental obesogens. The review aimed to provide information on currently available two-dimensional (2D) in vitro animal and human cell models applied for studying the mechanisms of obesogenic action of various industrial chemicals such as food contaminants. The advantages and limitations of in vitro models representing the crucial endocrine tissue (adipose tissue) and organs (liver and pancreas) involved in the etiology of obesity and metabolic diseases, which are applied to evaluate the effects of obesogenic EDCs and their disruption activity, were thoroughly and critically discussed.

A purified fraction of polysaccharides from the fruits of Lycium barbarum L. improves glucose homeostasis and intestinal barrier function in high-fat diet-fed mice.

High-fat diet (HFD) consumption can induce intestinal barrier dysfunction and disrupt glucose metabolism. Our previous studies have demonstrated that polysaccharides obtained from the fruits of Lycium barbarum L. (LBPs) could suppress acute experimental diabetes as well as colitis in mice. In the present study, the modulating effects of a purified fraction of LBPs, named LBPs-4, on glucose homeostasis and intestinal barrier function in mice fed with a HFD were investigated. Our results indicated that the oral administration of LBP-4 (200 mg per kg per day) improved hyperglycemia, glucose intolerance, insulin resistance and islet β-cell hyperplasia in HFD-fed mice. Moreover, LBPs-4 intervention enhanced the intestinal barrier integrity by increasing the expression levels of zonula occludens 1 and claudin-1 and the number of goblet cells in the colon. LBPs-4 also modulated the composition of gut microbiota by increasing the relative abundances of butyrate producer Allobaculum and acetate producer Romboutsia. The results of fecal transplantation experiments, transferring of microbiota from LBPs-4-fed donor mice to HFD-fed recipient mice, validated the cause-effect relationship between LBPs-4-evoked changes in the gut microbiota and improvement of glucose homeostasis and intestinal barrier function. Collectively, these findings suggested that LBPs-4 might be developed as promising prebiotics to improve glucose metabolism and gut health.

Ambient NO2 exposure affects hepatic glycolipid metabolism in mice with a sex-dependent property

NO 2 is one of the major air pollutants. Exposure to NO 2 is associated with various metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), diabetes, cardiovascular disease, etc. Abnormal hepatic glycolipid metabolism is a key feature of metabolic diseases. However, few studies provide evidence for the effects of NO 2 inhalation on hepatic glycolipid metabolism. In this study, female and male C57BL/6 J mice were exposed to NO 2 (2.5 ppm, 5 h/day) for 4 weeks using a systemic inhalation exposure system. The results indicated that NO 2 exposure increased the levels of hepatic enzymes in serum and led to liver dysfunction in female mice, but not male ones. Especially, female mice developed glycolipid metabolic disorders, including increased blood glucose, decreased hepatic glycogen and glucose tolerance, and increased lipid level in liver and blood. Metabolomic analysis clarified 33 differential metabolites of glycolipids, which were mainly enriched through several pathways, including synthesis and degradation of ketone bodies, fat digestion and absorption, galactose metabolism, fatty acid degradation, and glycerophospholipid metabolism. The mRNA and protein expression implicated that the exposure disrupted glucose metabolism by reducing hepatic glycogen synthesis and increasing gluconeogenesis, and caused lipid deposition by increasing lipogenesis and uptake, thereby increasing lipid oxidation and secretion. The findings highlight the risk of metabolic diseases upon exposure to NO 2 in the air. • NO 2 exposure caused female-specific hepatic glycolipid metabolism disorders. • NO 2 inhalation altered glycogen synthesis and gluconeogenesis. • NO 2 inhalation affected lipogenesis and uptake, and induced lipid deposition.

Magnesium-Rich Indonesian Brown Rice ‘Sintanur’ Improves Insulin Sensitivity in High Fat High Fructose Diet-Induced Obesity Sprague Dawley Rats

This study aimed to analyze the effect of 'Sintanur' brown rice on Lee's index, fasting blood glucose levels, and HOMA-IR administered to male Sprague Dawley rats. This research was an experimental laboratory study with a post-test-only control group design. The subjects were thirty-five male Sprague Dawley rats divided into five groups. Group 1 consisted of the negative control with a standard diet. Group 2 consisted of the positive control with HFFD-induced obesity for 20 weeks, while groups 3, 4, and 5 were the treatment groups with HFFD-induced obesity for 12 weeks, which were intervened with different dosages of brown rice diet from week 13 to week 20. At week 21, the rats were sacrificed. Fasting blood glucose levels were tested using a glucometer. Fasting serum insulin levels were tested using ELISA. HOMA-IR was calculated using fasting glucose and insulin levels. Serum magnesium levels were tested using Atomic Absorption Spectrophotometry. A non-parametric test of Kruskal-Wallis was used to analyze differences in mean dietary intake, Lee index, fasting blood glucose, and HOMA-IR. As a result, there were significant differences between groups (p<0.05). Spearman correlation test was used to analyze the relationship between the Lee index, fasting blood glucose levels, and HOMA-IR with serum magnesium levels. As a result, there were negative correlations between parameters (r=-0.299; r=-0.393; r=-0.257). Group 5 had the best results in lowering insulin resistance. In conclusion, consuming local 'Sintanur' brown rice decreased the Lee index, fasting blood glucose levels, and HOMA-IR by increasing serum magnesium levels in obese rats. High magnesium intake reduces insulin resistance by correcting the disruption of glucose metabolism and insulin signaling pathways.

Glucocorticoid-induced hyperglycemia (GIH) in pemphigus vulgaris patient at Bangli District General Hospital: A case report

Background: Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous blistering and erosion. This is rare, but greatly affects the patient’s life quality and often cause complication of disease and therapy. Hyperglycemia is a complication due to steroid use called glucocorticoid-induced hyperglycemia (GIH). This case report describes hyperglycemia in PV treatment, which later can be a consideration of PV management.
 Case: A 44-year-old male patient complained of painful lesions on almost the whole body with a form of bullae, erosion, crusting, brittle, the Nikolsky sign (+), and Asboe-Hansen sign (+). The patient was diagnosed with PV. After he had supportive therapy and high-doses of methylprednisolone, his blood sugar is increased. Patients diagnosed by hyperglycemia state due to steroid use, then given insulin as therapy. The patient diagnosed with PV based on history taking and physical examination, but the histopathologic examination wasn’t done due to lack of modality at the hospital. The steroid was given as an immunosuppressive. Be the main therapy for PV, steroids lead hyperglycemia due to disruption of glucose metabolism, thereby increasing insulin resistance in tissues. The diagnosis of hyperglycemia due to steroid use is made in a patient with a normal sugar level before PV therapy. It occurred within the first 1-2 days of therapy. In these patients, diagnosis confirmed by increasing pre-prandial, 2 h post-prandial, and any-time glucose level, after two days methylprednisolone administration. Collaboration with internal medicine colleagues is needed.
 Conclusion: PV treatment with steroids can induce hyperglycemia, which is dangerous. The understanding mechanism is needed to make early detection and provide therapy properly.

BDE-47, -99, -209 and Their Ternary Mixture Disrupt Glucose and Lipid Metabolism of Hepg2 Cells at Dietary Relevant Concentrations: Mechanistic Insight through Integrated Transcriptomics and Proteomics Analysis.

Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals implied as flame retardants. Humans are mainly exposed to BDE-47, -99, and -209 congeners by diet. PBDEs are metabolic disruptors with the liver as the main target organ. To investigate their mode of action at a human-relevant concentration, we exposed HepG2 cells to these congeners and their mixture at 1 nM, analyzing their transcriptomic and proteomic profiles. KEGG pathways and GSEA Hallmarks enrichment analyses evidenced that BDE-47 disrupted the glucose metabolism and hypoxia pathway; all the congeners and the MIX affected lipid metabolism and signaling Hallmarks regulating metabolism as mTORC1 and PI3K/AKT/MTOR. These results were confirmed by glucose secretion depletion and increased lipid accumulation, especially in BDE-47 and -209 treated cells. These congeners also affected the EGFR/MAPK signaling; further, BDE-47 enriched the estrogen pathway. Interestingly, BDE-209 and the MIX increased ERα gene expression, whereas all the congeners and the MIX induced ERβ and PPARα. We also found that PBDEs modulated several lncRNAs and that HNRNAP1 represented a central hub in all the four interaction networks. Overall, the PBDEs investigated affected glucose and lipid metabolism with different underlying modes of action, as highlighted by the integrated omics analysis, at a dietary relevant concentration. These results may support the mechanism-based risk assessment of these compounds in relation to liver metabolism disruption.

ODP604 | LBSUN287 Ketosis-prone Type 2 Diabetes (Flatbush Diabetes) In Remission: Report Of Two Cases

Abstract Diabetic ketoacidosis (DKA) is a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration1. Diabetic ketoacidosis (DKA) is a well-known manifestation of Type 1 diabetes2; however, there has been an increase in the incidence of DKA as the first presentation in Type 2 diabetes. This subtype of diabetes is typically seen in non-Caucasian middle-aged obese males due to non-autoimmune disruption of glucose metabolism, which requires an initial intensive insulin regimen. After initial insulin treatment for several weeks to several months, a significant percentage of people can become insulin independent with an oral hypoglycemic agent(OHA) and /or just lifestyle modification, and in remission for many years3. This hybrid form of diabetes sharing the characteristics of T1DM and T2DM is called "Flatbush diabetes", also known as "ketosis-prone T2DM4 5. This article aims to emphasize the importance of early recognition of this heterogeneous syndrome through the two representative case reports of Ketosis-prone T2DM. Case presentation We describe two cases of African American men (elderly and young adult) with no past medical histories, who presented to the Emergency Department with a few days history of polyphagia, polydipsia, polyuria and fatigue. New onset of Type 2 diabetes and unprovoked DKA were diagnosed. Both of them received standard treatment with intravenous fluid and insulin drip, recovered uneventfully and discharged with insulin. Both of them followed up closely in our endocrinology clinic, their GAD antibodies were 0. 00(n<=0. 02nmol/L), Islet cell antibody<1: 4(n<1: 4) and C-peptide were 2.6ng/mL and 6ng/mL(1.1-4.4ng/mL) respectively. Their insulin was gradually withdrawn with the addition of an oral hypoglycemic agent. Both the patients are currently insulin independent for more than 15 months. Conclusion This is an important clinical entity to recognize ketosis-prone T2DM as insulin independence positively impacts quality of life and decreases economic burden on the health care system. For patients with suspected ketosis-prone T2DM, B-cell autoantibodies and C-peptide level should be obtained 1-3 weeks at the first outpatient visit, as it can predict patients’ prognosis. These patients should also be referred to an endocrinologist and need careful follow-up. Among all ketosis-prone T2DM patients, those with preserved B-cell function are more likely to be insulin independent and go into remission phase. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Insufficient sleep disrupts glucose metabolism during pregnancy by inhibiting PGC-1α

Gestational diabetes mellitus (GDM) impacted about 17 million pregnancies globally and predisposes both the mother and her offspring to metabolic disorders. Insufficient sleep has been shown to be associated with GDM. This study aimed to explore the molecular link between sleep and GDM. The sleep of pregnant mice was disturbed with motion a rod and the mice received either dimethyl sulfoxide (DMSO) or ZLN005. Insulin resistance was assessed by intraperitoneal glucose tolerance test (GTT). Adenosine triphosphate (ATP), reactive oxygen species (ROS), and cytokines were measured with respective commercial kits. Gene expression was analyzed with quantitative polymerase chain reaction (qPCR), western blot, and/or immunohistochemistry (IHC). Sleep disturbance increased blood glucose level and insulin resistance, increased ROS and inflammatory cytokines, and reduced ATP level in pregnant mice. The expression levels of PGC-1α and downstream metabolic genes and antioxidant genes in pregnant mouse muscle were inhibited by sleep disturbance. ZLN005 promoted expression of PGC-1α and its target genes, increased muscle ATP level, decreased muscle ROS, and reduced blood glucose level and insulin resistance in sleep disturbed pregnant mice, indicating that PGC-1α played a critical role in sleep insufficiency caused GDM and might be a target for intervention. PGC-1 was a key player in the sleep disorder GDM and might be a target for treatment.

Uygur type 2 diabetes patient fecal microbiota transplantation disrupts blood glucose and bile acid levels by changing the ability of the intestinal flora to metabolize bile acids in C57BL/6 mice

BackgroundOur epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism.MethodsThe normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2 mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2 mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8 weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting.ResultsMT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-β-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly.ConclusionsUygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway.

Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity.

Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono–Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of Tbc1d1, Glut4, Hk2, Pfkm, Pdp1, Gbe1, and Phka1, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of Pdk4 and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity.

Fractions of Lawsonia inermis Linn leaves reversed the damage caused to major organs involved in diabetic complications by improving their histomorphological appearance in diabetic Wistar rat model

Diabetes mellitus (DM) is clinically known as diverse sets of biochemical syndromes with a basic symptom of glucose intolerance and is a major cause of morbidity and mortality worldwide. Diabetes mellitus exclusively disrupts glucose metabolism in various tissues and organs leading to complications such as retinopathy, nephropathy and brain micro-infarcts. This study investigated the positive modulatory effect of Lawsonia inermis Linn leaves on major organs involved in diabetic complications in Wister rats experimentally induced by type 1 diabetes using streptozocine. Lawsonia inermis leaves were partitioned using N-hexane, ethyl acetate and methanol. Fractions obtained were assessed for their modulatory potential. Seven groups of diabetic rats (n=5) were orally administered 100mg/kg of each of the three partitioned fractions, metformin (500mg/kg), glibenclamide (5mg/kg), while untreated hyperglycaemic and normoglycaemic rats received distilled water (ad libitum) daily for 28 days. Mean relative organ weight of the brain, heart, kidney, pancreas and liver increased significantly (p<0.05) in untreated diabetic rats when compared to Lawsonia inermis treated rats and non-diabetic control. Diabetic treated rats showed non-significant (p>0.05) increased weight in all the organs except the pancreas that decreased non-significantly when compared to normoglycemic rats. The histopathology results showed that Lawsonia inermis improved the organ damage seen in diabetic complications through prevention of organomegaly and improvement in histoarchitectural appearance that is devoid of lesions when compared to untreated diabetic control with various lesions. Conclusively, Lawsonia inermis Linn leaves improve significant reduction in organ damage during course of Type 1 diabetes mellitus.

ITRAQ-based quantitative proteomic analysis in liver of Pomacea canaliculata induced by oleanolic acid stress.

Triterpene acid is one of the typical active constituents of Eucalyptus bark, which is the main by-product of the Eucalyptus wood industry. Our studies have demonstrated that triterpene acid stress could inhibit climbing and increase mortality in Pomacea canaliculata (Lamarck). However, limited attention has been paid to the proteomic responses of this snail under triterpene acid stress. Using iTRAQ-based quantitative proteomics, we elucidated the regulatory mechanism in the livers of P. canaliculata held in chlorine-free water and exposed to 100 mg L-1 oleanolic acid (OA) for 24 h. A total of 4308 proteins were identified, of which 274 were differentially expressed proteins (DEPs) including 168 (61.31%) differentially upregulated proteins and 106 (38.69%) differentially downregulated proteins. Bioinformatics analysis revealed that P. canaliculata responses to OA stress are mainly involved in glucose metabolism, energy synthesis, immune response, stress response, protein synthesis, and apoptosis. According to KEGG analysis, the 274 DEPs were mapped to 168 KEGG pathways and 10 KEGG pathways were significantly enriched (P < 0.05). Furthermore, qRT-PCR was performed for histone H4, catalase, isocitrate dehydrogenase, superoxide dismutase, ferritin, lipase, and tropomyosin to validate the iTRAQ results. Proteomic analysis suggested that OA stress led to the disruption of glucose metabolism, energy synthesis, and protein synthesis, and triggered a series of molecular pathways containing many key proteins involved in the immune process, thereby helping P. canaliculata resist OA stress. © 2022 Society of Chemical Industry.

1341-P: Dietary Fat and Fructose Impair Glucagon-Stimulated Liver Glucose Metabolism

High fat and fructose diets (HFFD) disrupt glucose metabolism. The aim of this study was to determine the effect of HFFD on glucagon (GGN) effectiveness. Dogs were fed either chow or HFFD for one month. After a basal sampling period, somatostatin and basal portal vein infusions of insulin and GGN were given for 4h, with the exception of GGN, which was either maintained at basal or increased 6-fold. Glucose was infused in the basal GGN groups (CHOW+GLC &amp; HFFD+GLC) to match the 3-fold increase in plasma glucose that occurred with 6x-GGN (CHOW+GGN &amp; HFFD+GGN) . There were no differences in plasma insulin or glucose and GGN levels were proportional to GGN infusion rates in all groups. 6x-GGN caused an identical increase in net hepatic glucose balance (NHGB) in the chow and HFFD groups (Fig 1A) after which NHGB declined. During the last hour NHGB was 1.8-fold greater in HFHF+GGN compared to Chow+GGN (A) . However, hyperglycemia per se caused a switch from net hepatic glucose output to uptake in Chow+GLC but not HFHF+GLC (there was a 3.7±0.4 vs. 0.3±0.4 mg/kg/min decrease in NHGB over time in the two groups, respectively) (B) . Thus, when expressed relative to each group’s respective glucose control group, the AUC for GGN stimulated NHGB was 1.9-fold greater in the Chow (C) compared to HFHF (D) groups (P&amp;lt;0.05) . In summary, HFHF feeding reduced hepatic glucagon action indirectly by impairing hepatic glucose effectiveness. Disclosure D.S.Edgerton: None. G.Kraft: None. K.C.Coate: None. B.Farmer: None. M.S.Smith: None. M.Scott: None. J.R.Hastings: None. M.C.Moore: None. A.D.Cherrington: Advisory Panel; Biocon, Diakard, Metavention, Sekkei Bio, Sensulin Labs, LLC, vTv Therapeutics, Consultant; Abvance, Fractyl Health, Inc., Novo Nordisk, Research Support; Bristol-Myers Squibb Company. Funding NIH R01DK18243

Efek Prolonged Sitting Saat Work from Home (WFH) Pada Para Pekerja Selama Pandemik Covid-19

Covid-19 pandemic situation has led to working pattern changes to working from home. The implementation of WFH led to a significant increase in the duration of sitting among workers which then induce physical inactivity. Physical inactivity. characterized by prolonged sitting generated several impacts on various aspect of body function and movement, including the musculoskeletal system, metabolism, immunity, inflammation and oxidative stress. This article aims to further analyze the effects of prolonged sitting on human’s body system organs and function. Previous study proved that prolonged sitting during WFH led to increase pain in the neck, shoulders, upper back and lower back regions. Moreover, prolonged sitting also induced insulin resistance conditions which disrupt glucose metabolism. Furthermore, prolonged sitting was able to enhance various biomarker of inflammation, as long as oxidative stress. meanwhile, active breaks with light to moderate intensity activities, during prolonged sitting proved to significantly increase the body’s immune markers and anti-oxidant defense. Thus, the implementation of WFH should be interspersed with low to moderate intensity of physical activity

Bacteroides ovatus-mediated CD27- MAIT cell activation is associated with obesity-related T2D progression.

Type 2 diabetes (T2D) is highly associated with obesity. However, the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial metabolites, have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity. By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D, we found an elevation in CD27-negative (CD27-) MAIT cells producing a high level of IL-17 under T2D obese conditions, which could be positively correlated with impaired glucose metabolism in obese people. We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities. Specifically, accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17-producing CD27- MAIT cell expansion and could be associated with T2D risk in obese individuals. Overall, these results suggest that an aberrant gut microbiota-immune axis in obese people may drive or exacerbate T2D. Importantly, CD27- MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies. Our findings extend current knowledge regarding the clinical relevance of body mass index (BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

A human prefrontal cortex tissue microarray to study Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by proteinopathy, glucose hypometabolism, progressive neurodegeneration and eventually death from organ failure. One of the disease characteristics is glucose hypometabolism in the brain that can lead to perturbed cerebral glycan and glycogen metabolism. A key driver of disrupted glucose metabolism could be linked to glycans, which is a co‐translational modification of proteins involved in various biological functions of the cell. Prior research has demonstrated profound glycosylation differences in AD tissue compared to normal tissue, however, these differences have yet to be linked to disease progression. In collaboration with AD biobank at the University of Kentucky led by Dr. Peter Nelson, human AD brain tissue samples from over 90 deceased patients with and without known cognitive impairment were collected, in addition to their corresponding metadata. To analyze the N‐linked glycan content of the samples a Tissue Microarray (TMA) was produced using cores punched from the patients’ cortex tissue, and run through an optimized, enzyme‐assisted matrix‐assisted laser desorption/ionization‐mass spectrometer imager (MALDI‐MSI) workflow. Our data not only revealed interesting correlations between glycosylation and disease pathology of AD but also interesting differences in the glycan profiles between male and female patients. Further indepth analyses will be required to further determine specific markers for the correlation between glycosylation and disease progression of AD.

Fractions of Lawsonia inermis Linn leaves improved the histomorphological appearance of major organs involved in diabetic complications

Diabetes mellitus (DM) is clinically known as diverse sets of biochemical syndromes with a basic symptom of glucose intolerance and is a major cause of morbidity and mortality worldwide. Diabetes mellitus exclusively disrupts glucose metabolism in various tissues and organs leading to complications such as retinopathy, nephropathy and brain micro-infarcts. This study investigated the positive modulatory effect of Lawsonia inermis Linn leaves on major organs involved in diabetic complications in Wister rats experimentally induced by type 1 diabetes using streptozocine. Lawsonia inermis leaves were partitioned using N-hexane, ethyl acetate and methanol. Fractions obtained were assessed for their modulatory potential. Seven groups of diabetic rats (n=5) were orally administered 100mg/kg of each of the three partitioned fractions, metformin (500mg/kg), glibenclamide (5mg/kg), while untreated hyperglycaemic and normoglycaemic rats received distilled water (ad libitum) daily for 28 days. Mean relative organ weight of the brain, heart, kidney, pancreas and liver increased significantly (p&lt;0.05) in untreated diabetic rats when compared to Lawsonia inermis treated rats and non-diabetic control. Diabetic treated rats showed non-significant (p&gt;0.05) increased weight in all the organs except the pancreas that decreased non-significantly when compared to normoglycemic rats. The histopathology results showed that Lawsonia inermis improved the organ damage seen in diabetic complications through prevention of organomegaly and improvement in histoarchitectural appearance that is devoid of lesions when compared to untreated diabetic control with various lesions. Conclusively, Lawsonia inermis Linn leaves improve significant reduction in organ damage during course of Type 1 diabetes mellitus.

Insights on the disruption of glucose metabolism and hepatic insulin resistance induced by hepatitis C virus

Hepatitis C virus (HCV) is still considered as a major public health problem because in 2015 around 71 million people were chronically infected worldwide. It is important to note that chronic HCV infection is a systemic disease that is associated with diverse extrahepatic disorders including insulin resistance and type 2 diabetes mellitus. The discovery of new direct-acting antiviral agents (DAAs) has become a huge advance in the treatment of HCV infection. The complex interplay between HCV and glucose metabolic pathways remains to be fully elucidated, but it is becoming clearer that elimination of chronic HCV infection halts the progression of liver disease, but more evidence is still needed to better understand how successful antiviral treatment influences insulin resistance and other abnormalities of glucose metabolism linked to HCV infection. This review provides a comprehensive overview of the glucose metabolism disturbances related to chronic HCV infection, highlighting the new insights into the molecular basis of insulin resistance induced by HCV and the mechanisms underlying the reversion of this metabolic disorder by DAAs.