Erratum. The First Genome-Wide Association Study for Type 2 Diabetes in Youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortium. Diabetes 2021;70: 996 –1005
The authors regret that an error was inadvertantly introduced in Table 1 while copying data from the original data files to the article cited above. For the case subjects, adult control subjects, and youth control subjects, respectively, the following mean ± SD data were presented: fasting glucose (mg/dL) 110.44 ± 23.86, not available (N/A), 110.44 ± 23.86; fasting insulin (μU/mL) 30.93 ± 22.33, N/A, 30.93 ± 22.33; and HbA1c % (mmol/mol) 6.01 (42) ± 0.75 (5.8), 7.53 (59) ± 2.32 (16.2), 6.73 (50) ± 1.84 (17.8). The correct data for these subjects are fasting glucose (mg/dL) 154.36 ± 88.99, 87.93 ± 10.61, 84.20 ±...
Source: Diabetes - October 29, 2021 Category: Endocrinology Source Type: research
Erratum. SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans. Diabetes 2021;70: 2364 –2376
In Table 2 of the above-cited article, the data column for placebo group (N = 20) for the single ascending dose (SAD) part of the study did not fall under the SAD column heading due to a composition error. The SAD part of the study included this placebo group. (Source: Diabetes)
Source: Diabetes - October 29, 2021 Category: Endocrinology Source Type: research
Glucagon Clearance Is Preserved in Type 2 Diabetes
In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes. (Source: Diabetes)
Source: Diabetes - October 26, 2021 Category: Endocrinology Source Type: research
Loss of Functional SCO2 Attenuates Oxidative Stress in Diabetic Kidney Disease
Increased oxidative stress in glomerular endothelial cells (GEnCs) contributes to early diabetic kidney disease (DKD). While mitochondrial respiratory complex IV activity is reduced in DKD, it remains unclear whether it is a driver or a consequence of oxidative stress in GEnCs. Synthesis of cytochrome C oxidase 2 (SCO2), a key metallochaperone in the electron transport chain, is critical to the biogenesis and assembly of subunits required for functional respiratory complex IV activity. Here, we investigated the effects ofSco2 hypomorphs (Sco2KO/KI,Sco2KI/KI), with a functional loss of SCO2, in the progression of DKD by usi...
Source: Diabetes - October 26, 2021 Category: Endocrinology Source Type: research
Impact of Proinflammatory Cytokines on Alternative Splicing Patterns in Human Islets
Alternative splicing (AS) within the β-cell has been proposed as one potential pathway that may exacerbate autoimmunity and unveil novel immunogenic epitopes in type 1 diabetes (T1D). We used a computational strategy to prioritize pathogenic splicing events in human islets treated with interleukin-1β plus interferon-γ as an ex vivo model of T1D and coupled this analysis with a k-mer–based approach to predict RNA-binding proteins involved in AS. In total, 969 AS events were identified in cytokine-treated islets, with a majority (44.8%) involving a skipped exon. ExonImpact identified 129 events predicted to affect prote...
Source: Diabetes - October 25, 2021 Category: Endocrinology Source Type: research
JMJD8 Is a Novel Molecular Nexus Between Adipocyte-Intrinsic Inflammation and Insulin Resistance
In this study, we demonstrate a novel role for Jumonji C domain-containing protein 8 (JMJD8) as an adipocyte-intrinsic molecular nexus between inflammation and insulin resistance. We determined that JMJD8 was highly enriched in white adipose tissue, especially in the adipocyte fraction. Adipose JMJD8 levels were dramatically increased in obesity-associated insulin resistance models. Its levels were increased by feeding and insulin and inhibited by fasting. A JMJD8 gain-of-function was sufficient to drive insulin resistance, whereas loss-of-function improved insulin sensitivity in mouse and human adipocytes. Consistent with...
Source: Diabetes - October 22, 2021 Category: Endocrinology Source Type: research
Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19
This study provides sc ientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target. (Source: Diabetes)
Source: Diabetes - October 22, 2021 Category: Endocrinology Source Type: research
COVID-19 –Induced New-Onset Diabetes: Trends and Technologies
The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. CO...
Source: Diabetes - October 22, 2021 Category: Endocrinology Source Type: research
Hepatic p38 Activation Modulates Systemic Metabolism Through FGF21-Mediated Interorgan Communication
In conclusion, our study reveals previously undescribed effects of hepatic p38 activation on systemic metabolism and provides new insights into the roles of hepatic p38α, FGF21, and β-Klotho in the pathogenesis of nonalcoholic fatty liver disease. (Source: Diabetes)
Source: Diabetes - October 21, 2021 Category: Endocrinology Source Type: research
Specific Deletion of CASK in Pancreatic β-Cells Affects Glucose Homeostasis and Improves Insulin Sensitivity in Obese Mice by Reducing Hyperinsulinemia
Calcium/calmodulin-dependent serine protein kinase (CASK) is involved in the secretion of insulin vesicles in pancreatic β-cells. The current study revealed a new in vivo role of CASK in glucose homeostasis during the progression of type 2 diabetes mellitus (T2DM). A Cre-loxP system was used to specifically delete theCask gene in mouse β-cells (βCASKKO), and glucose metabolism was evaluated in βCASKKO mice fed a normal chow diet (ND) or a high-fat diet (HFD). ND-fed mice exhibited impaired insulin secretion in response to glucose stimulation. Transmission electron microscopy showed significantly reduced numbers of insu...
Source: Diabetes - October 21, 2021 Category: Endocrinology Source Type: research
EET Analog Treatment Improves Insulin Signaling in a Genetic Mouse Model of Insulin Resistance
We previously showed that global deletion of the cytochrome P450 epoxygenaseCyp2c44, a major epoxyeicosatrienoic acid (EET) –producing enzyme in mice, leads to impaired hepatic insulin signaling resulting in insulin resistance. This finding led us to investigate whether administration of a water-soluble EET analog restores insulin signaling in vivo inCyp2c44−/− mice and investigated the underlying mechanisms by which this effect is exerted.Cyp2c44−/− mice treated with the analog disodium 13-(3-pentylureido)tridec-8(Z)-enoyl)-LL-aspartate2 (EET-A) for 4 weeks improved fasting glucose and glucose tolerance compared...
Source: Diabetes - October 21, 2021 Category: Endocrinology Source Type: research
Hepatic CPT1A Facilitates Liver –Adipose Cross Talk via Induction of FGF21 in Mice
In this study, we use hepatocyte-specificCpt1a knockout (LKO) mice to investigate the physiological consequences of abolishing hepatic long-chain fatty acid metabolism. Compared with the wild-type littermates, high-fat diet (HFD) –fed LKO mice displayed more severe hepatosteatosis but were otherwise protected against diet-induced weight gain, insulin resistance, hepatic endoplasmic reticulum stress, inflammation, and damage. Interestingly, increased energy expenditure was observed in LKO mice, accompanied by enhanced adipo se tissue browning. RNA-sequencing analysis revealed that the peroxisome proliferator–activated r...
Source: Diabetes - October 21, 2021 Category: Endocrinology Source Type: research
Relationship Between Insulin Secretion and Insulin Sensitivity and Its Role in Development of Type 2 Diabetes: Beyond the Disposition Index
We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all participants did not have diabetes, 1,566 underwent oral tests and 420 had intravenous measures of glucose regulation, with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship between secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relati...
Source: Diabetes - October 18, 2021 Category: Endocrinology Source Type: research
Active Brown Adipose Tissue Is Associated With a Healthier Metabolic Phenotype in Obesity
Obesity is associated with increasing cardiometabolic morbidity and mortality rates worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested to be a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in people with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with World Health Organization class II-III obesity (BMI ≥35 kg/m2). Using a 150-min personalized cooling protocol and18F-fluorodeoxyglucose (18F-FDG) positro...
Source: Diabetes - October 18, 2021 Category: Endocrinology Source Type: research
Novel Human Insulin Isoforms and C α-Peptide Product in Islets of Langerhans and Choroid Plexus
Human insulin (INS) gene diverged from the ancestral genes of invertebrate and mammalian species millions of years ago. We previously found that mouse insulin gene (Ins2) isoforms are expressed in brain choroid plexus (ChP) epithelium cells, where insulin secretion is regulated by serotonin and not by glucose. We further compared humanINS isoform expression in postmortem ChP and islets of Langerhans. We uncovered novelINS upstream open reading frame isoforms and their protein products. In addition, we found a novel alternatively spliced isoform that translates to a 74 –amino acid (AA) proinsulin containing a shorter 19-A...
Source: Diabetes - October 14, 2021 Category: Endocrinology Source Type: research
