Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.
Endocrine Reviews 37(3):190 (2016)
To date, more than 30 genes have been linked to monogenic diabetes. Candidate gene and genome-wide association studies have identified > 50 susceptibility loci for common type 1 diabetes (T1D) and approximately 100 susceptibility loci for type 2 diabetes (T2D). About 1-5% of all cases of diabete...
Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina.
Journal of Biological Chemistry 291(9):4698 (2016)
Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternative...
Ablation of a small subpopulation of diabetes-specific bone marrow-derived cells in mice protects against diabetic neuropathy.
American Journal of Physiology - Endocrinology ... 310(4):E269 (2016)
Diabetic peripheral neuropathy (DPN) is a major diabetic complication. Previously, we showed that hyperglycemia induces the appearance of proinsulin (PI)-producing bone marrow-derived cells (PI-BMDCs), which fuse with dorsal root ganglion neurons, causing apoptosis, nerve dysfunction, and DPN. I...
Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells.
Advances in Experimental Medicine and Biology 854:549 (2016)
Interest in generating human induced pluripotent stem (iPS) cells for stem cell modeling of diseases has overtaken that of patient-specific human embryonic stem cells due to the ethical, technical, and political concerns associated with the latter. In ophthalmology, researchers are currently usi...
ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity.
Scientific reports 6:29669 (2016)
Irisin reportedly promotes the conversion of preadipocytes into "brown-like" adipocytes within subcutaneous white adipose tissue (WAT) via a mechanism that stimulates UCP-1 expression. An increase in plasma irisin has been associated with improved obesity and insulin resistance in mice with type...
ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in β-Cell Line.
PLoS ONE 11(1):e0147411 (2016)
Carbohydrate response element binding protein (ChREBP) is an important transcription factor that regulates a variety of glucose-responsive genes in hepatocytes. To date, only two natural isoforms, Chrebpα and Chrebpβ, have been identified. Although ChREBP is known to be expressed in pancreatic β...
Mammalian autophagy is essential for hepatic and renal ketogenesis during starvation.
Scientific reports 6:18944 (2016)
Autophagy is an intracellular degradation system activated, across species, by starvation. Although accumulating evidence has shown that mammalian autophagy is involved in pathogenesis of several modern diseases, its physiological role to combat starvation has not been fully clarified. In this s...
Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer.
Nature Communications 7:11612 (2016)
The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme gl...
The ERα-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice.
Endocrinology 156(12):4474 (2015)
Estrogens act upon estrogen receptor (ER)α to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ER...
FABP4-Cre Mediated Expression of Constitutively Active ChREBP Protects Against Obesity, Fatty Liver, and Insulin Resistance.
Endocrinology 156(11):4020 (2015)
Carbohydrate response element binding protein (ChREBP) regulates cellular glucose and lipid homeostasis. Although ChREBP is highly expressed in many key metabolic tissues, the role of ChREBP in most of those tissues and the consequent effects on whole-body glucose and lipid metabolism are not we...
Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes.
Molecular Endocrinology 29(9):1320 (2015)
Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for ...
Rapid resolution of retinoschisis with acetazolamide.
Documenta Ophthalmologica 131(1):63 (2015)
To report the results of an acetazolamide (Diamox(®)) treatment regimen in a genetically confirmed case of X-linked juvenile retinoschisis (XLRS).
A patient with XLRS was prescribed acetazolamide (Diamox(®)) at a dose of 500 mg/day, then discontinued the treatment due to non-compliance for 4 day...
Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice.
FASEB Journal 29(8):3537 (2015)
Adipose tissue macrophages (ATMs) play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet (HFD)-induced obesity has been shown to lead to ATM accumulation in rodents; however, the impact of hyperglycemia on ATM dynamics in HFD-fed type 2 diabetic models has not been st...
Erratum. PD-L1-Driven Tolerance Protects Neurogenin3-Induced Islet Neogenesis to Reverse Established Type 1 Diabetes in NOD Mice. Diabetes 2015;64:529-540.
Diabetes 64(7):2685 (2015)
Genome-Wide Analysis of ChREBP Binding Sites on Male Mouse Liver and White Adipose Chromatin.
Endocrinology 156(6):1982 (2015)
Glucose is an essential nutrient that directly regulates the expression of numerous genes in liver and adipose tissue. The carbohydrate response element-binding protein (ChREBP) links glucose as a signaling molecule to multiple glucose-dependent transcriptional regulatory pathways, particularly ...
PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice.
Diabetes 64(2):529 (2015)
A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. A cure by restoring β-cell mass is limited by the availability of transplantable β-cells and the need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through the PD-1/PD...
Bone marrow-derived TNF-α causes diabetic neuropathy in mice.
Diabetologia 58(2):402 (2015)
Dysregulation of biochemical pathways in response to hyperglycaemia in cells intrinsic to the nervous system (Schwann cells, neurons, vasa nervorum) are thought to underlie diabetic peripheral neuropathy (DPN). TNF-α is a known aetiological factor; Tnf-knockout mice are protected against DPN. We...
Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.
PLoS ONE 10(6):e0128996 (2015)
We tested whether a high fat diet (HFD) containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/-) mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDA...
Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model.
Nature Communications 6:7339 (2015)
Diseases of lipid metabolism are a major cause of human morbidity, but no animal model entirely recapitulates human lipoprotein metabolism. Here we develop a xenograft mouse model using hepatocytes from a patient with familial hypercholesterolaemia caused by loss-of-function mutations in the low...
MondoA deficiency enhances sprint performance in mice.
Biochemical Journal 464(1):35 (2014)
MondoA is a basic helix-loop-helix (bHLH)/leucine zipper (ZIP) transcription factor that is expressed predominantly in skeletal muscle. Studies in vitro suggest that the Max-like protein X (MondoA:Mlx) heterodimer senses the intracellular energy status and directly targets the promoter region of...