Journal: Diabetes

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American Diabetes Association

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ISSN

0012-1797
1939-327X

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Publications 1 - 10 of 14
  • Regulation of Apolipoprotein M Gene Expression by MODY3 Gene Hepatocyte Nuclear Factor–1α: Haploinsufficiency is associated with reduced serum apoM levels
    Item type: Journal Article
    Richter, Symi; Shih, David Q.; Pearson, Ewan R.; et al. (2003)
    Diabetes
  • Dietary phytoestrogens activate AMP
    Item type: Journal Article
    Cederroth, Christopher R.; Vinciguerra, Manlio; Gjinovci, Asllan; et al. (2008)
    Diabetes
  • Nogo-A Downregulation Improves Insulin Secretion in Mice
    Item type: Journal Article
    Bonal, Claire B.; Baronnier, Delphine E.; Pot, Caroline; et al. (2013)
    Diabetes
    Type 2 diabetes (T2D) is characterized by β-cell dysfunction and the subsequent depletion of insulin production, usually in a context of increased peripheral insulin resistance. T2D patients are routinely treated with oral antidiabetic agents such as sulfonylureas or dipeptidyl peptidase-4 antagonists, which promote glucose- and incretin-dependent insulin secretion, respectively. Interestingly, insulin secretion may also be induced by neural stimulation. Here we report the expression of Nogo-A in β-cells. Nogo-A is a membrane protein that inhibits neurite outgrowth and cell migration in the central nervous system. We observed that Nogo-A–deficient mice display improved insulin secretion and glucose clearance. This was associated with a stronger parasympathetic input and higher sensitivity of β-cells to the cholinergic analog carbachol. Insulin secretion was also improved in diabetic db/db mice treated with neutralizing antibody against Nogo-A. Together, these findings suggest that promoting the vagal stimulation of insulin secretion through the selective inhibition of Nogo-A could be a novel therapeutic approach in T2D.
  • Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats
    Item type: Journal Article
    Clegg, Deborah J.; Brown, Lynda M.; Zigman, Jeffrey M.; et al. (2007)
    Diabetes
  • Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes
    Item type: Journal Article
    Challa, Tenagne D.; Straub, Leon G.; Balaz, Miroslav; et al. (2015)
    Diabetes
  • AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits
    Item type: Journal Article
    Treebak, Jonas T.; Glund, Stephan; Deshmukh, Atul; et al. (2006)
    Diabetes
  • A Machine Learning–Based Approach to Noninvasively Detect Hypoglycemia from Gaze Behavior While Driving
    Item type: Other Conference Item
    Lehmann, Vera; Maritsch, Martin; Züger, Thomas; et al. (2021)
    Diabetes
    Aim: To non-invasively detect hypoglycemia in individuals with type 1 diabetes (T1D) based on gaze behavior while driving. Methods: Controlled hypoglycemia was induced in 19 individuals (12 males, age 32 ± 7.1 yrs) with T1D (HbA1c 7.1 ± 0.6% [54 ± 6 mmol/mol]) using an adapted hypoglycemic clamp protocol. Gaze and blood glucose (BG) data were gathered while driving in a simulator during three 18 min sessions: session 1 (BG 90-144 mg/dL), session 2 (BG declining from 72 to 45 mg/dL), and session 3 (BG 36-45 mg/dL). A gradient-boosting machine learning (ML) model was built for hypoglycemia (BG < 70 mg/dL) detection based on gaze behavior. Results: Mean venous BG was 105.4 ± 11.4 mg/dL during session 1, declined from 61.4 ± 6.1 mg/dL to 47.2 ± 8.5 mg/dL during session 2, and was 42.7 ± 4.1 mg/dL during session 3, respectively. Gaze analysis provided 29,968 data samples (1,577.5 ± 52 per subject, 10,041 euglycemia, 19,927 hypoglycemia). Overall, ML achieved an area under the receiver-operating-characteristics curve of 0.83 ± 0.09 for hypoglycemia detection with leave-one-subject-out cross-validation. Conclusion: ML-based gaze analysis shows high accuracy in non-invasive hypoglycemia detection while driving. Our approach offers promising potential in various settings where cameras are available.
  • Beneficial Metabolic Effects of TREM2 in Obesity Are Uncoupled From Its Expression on Macrophages
    Item type: Journal Article
    Sharif, Omar; Brunner, Julia Stefanie; Korosec, Ana; et al. (2021)
    Diabetes
    Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health.
  • Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes
    Item type: Journal Article
    Hiller, Helmut; Beachy, Dawn E.; Lebowitz, Joseph J.; et al. (2021)
    Diabetes
    Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for T1D would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by nonredundant single-gene mutations. Using a "monogenetic transcriptomic strategy," we measured the expression of these genes in human T1D, autoantibody-positive (autoantibody+), and control pancreas tissues with real-time quantitative PCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Gene and protein expression was visualized in situ with use of immunofluorescence, RNAscope, and confocal microscopy. Two dozen monogenic diabetes genes showed altered expression in human pancreata from individuals with T1D versus unaffected control subjects. Six of these genes also saw dysregulation in pancreata from autoantibody+ individuals at increased risk for T1D. As a subset of these genes are related to cellular stress responses, we measured integrated stress response (ISR) genes and identified 20 with altered expression in T1D pancreata, including three of the four eIF2α-dependent kinases. Equally intriguing, we observed significant repression of the three arms of the ISR in autoantibody+ pancreata. Collectively, these efforts suggest monogenic diabetes and ISR genes are dysregulated early in the T1D disease process and likely contribute to the disorder's pathogenesis.
  • Metabolomics identifies a biomarker revealing in vivo loss of functional ß-cell mass before diabetes onset
    Item type: Journal Article
    Li, Lingzi; Krznar, Petra; Erban, Alexander; et al. (2019)
    Diabetes
    Identification of pre-diabetic individuals with decreased functional ß-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic ß-cell defect remains unsuccessful. Metabolomics emerged as a powerful tool in providing read-outs of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional ß-cell mass in the asymptomatic pre-diabetic stage. Non-targeted and targeted metabolomics were applied on both lean ß-Phb2-/- mice (ß-cell-specific prohibitin-2 knockout) and obese db/db mice (leptin receptor mutant), two distinct mouse models requiring neither chemical nor diet treatments to induce spontaneous decline of functional ß-cell mass promoting progressive diabetes development. Non-targeted metabolomics on ß-Phb2-/- mice identified 48 and 82 significantly affected metabolites in liver and plasma, respectively. Machine learning analysis pointed to deoxyhexose sugars consistently reduced at the asymptomatic pre-diabetic stage, including in db/db mice, showing strong correlation with the gradual loss of ß-cells. Further targeted metabolomics by GC-MS uncovered the identity of the deoxyhexose with 1,5-anhydroglucitol displaying the most significant changes. In conclusion, this study identified 1,5-anhydroglucitol associated with the loss of functional ß-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in ß-cells.
Publications 1 - 10 of 14