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NIDDK Grantee News

Sep 8, 2015

Previous studies have shown increasing prevalence of diabetes in the United States. New US data are available to estimate prevalence of and trends in diabetes.

NIDDK Grantee News

Sep 1, 2015

Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota.

NIDDK Grantee News

Aug 31, 2015

Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution.

NIDDK Grantee News

Aug 24, 2015

Traditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD.

NIDDK Grantee News

Aug 20, 2015

Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota.

NIDDK Grantee News

Aug 4, 2015

The mechanisms underlying the development of complications in type 1 diabetes (T1D) are poorly understood. Disease modeling of induced pluripotent stem cells (iPSCs) from patients with longstanding T1D (disease duration ≥ 50 years) with severe (Medalist +C) or absent to mild complications (Medalist −C) revealed impaired growth, reprogramming, and differentiation in Medalist +C.

NIDDK Grantee News

Jul 21, 2015

Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects.

NIDDK Grantee News

Jul 20, 2015

Chronic kidney disease is characterized by interstitial fibrosis and proliferation of scar-secreting myofibroblasts, ultimately leading to end-stage renal disease.

NIDDK Grantee News

Jul 2, 2015

SNPs affecting disease risk often reside in non-coding genomic regions. Here, we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARγ, a nuclear receptor for anti-diabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors and functionally regulate nearby genes whose expression is strain selective and imbalanced in heterozygous F1 mice.

NIDDK Grantee News

Jul 1, 2015

Activation of estrogen receptor α (ERα) in the brain prevents obesity as the result of increased energy expenditure and decreased food intake. While ERα is present on several neural populations, it is not clear how different regions of the brain mediate the weight-regulating effects of ERα activation.

NIDDK Grantee News

Jun 29, 2015

It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men.

NIDDK Grantee News

Jun 22, 2015

Estrogens play critical roles in the regulation of energy homeostasis. Depletion of endogenous estrogens in female rodents, via ovariectomy (OVX), causes increased body weight and hyperadiposity (1,2). 17β-estradiol replacement can prevent obesity in OVX female animals (1).

NIDDK Grantee News

Jun 18, 2015

Little is known about renin-angiotensin-aldosterone system (RAAS) activation in relationship to visceral adipose tissue (VAT) accumulation in HIV-infected patients, a population at significant risk for insulin resistance and other metabolic disease.

NIDDK Grantee News

May 6, 2015

Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder of unknown etiology affecting the extrahepatic biliary tree of neonates. Epidemiological studies suggest that an environmental factor, such as a virus or toxin, is the cause of the disease, although none have been definitively established.

NIDDK Grantee News

Apr 1, 2015

Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range.

NIDDK Grantee News

Mar 14, 2015

The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis.

NIDDK Grantee News

Mar 12, 2015

Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity.

NIDDK Grantee News

Mar 5, 2015

Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. Here we test whether CB1R-controlled feeding in sated mice is paralleled by decreased activity of POMC neurons.

NIDDK Grantee News

Feb 26, 2015

Hunger is controlled by specialized neural circuits that translate homeostatic needs into motivated behaviors. These circuits are under chronic control by circulating signals of nutritional state, but their rapid dynamics on the timescale of behavior remain unknown.

NIDDK Grantee News

Feb 24, 2015

Urinary tract infections (UTIs) are among the most common bacterial infections, causing considerable morbidity in females. Infection is highly recurrent despite appropriate antibiotic treatment.

NIDDK Grantee News

Feb 21, 2015

The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis.

NIDDK Grantee News

Feb 1, 2015

Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells.

NIDDK Grantee News

Feb 1, 2015

The goal of this study was to determine if Head Start participation is associated with healthy changes in BMI.

NIDDK Grantee News

Jan 29, 2015

Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients.

NIDDK Grantee News

Jan 15, 2015

Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined.

NIDDK Grantee News

Jan 15, 2015

Hematopoietic stem and progenitor cells (HSPCs) can reconstitute and sustain the entire blood system. We generated a highly specific transgenic reporter of HSPCs in zebrafish.

NIDDK Grantee News

Jan 15, 2015

Obesity-linked insulin resistance is a major precursor to the development of type 2 diabetes. Previous work has shown that phosphorylation of PPARγ (peroxisome proliferator-activated receptor γ) at serine 273 by cyclin-dependent kinase 5 (Cdk5) stimulates diabetogenic gene expression in adipose tissues. Inhibition of this modification is a key therapeutic mechanism for anti-diabetic drugs that bind PPARγ, such as the thiazolidinediones and PPARγ partial agonists or non-agonists.

NIDDK Grantee News

Jan 6, 2015

To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.

NIDDK Grantee News

Jan 6, 2015

Estrogen-receptor alpha (ERα) neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL) control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction.

NIDDK Grantee News

Jan 1, 2015

Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms by inducing fibrosis. We previously used a well-characterized mouse model of bacterial-induced prostate inflammation to demonstrate that chronic prostatic inflammation induces collagen deposition.

NIDDK Grantee News

Dec 26, 2014

Obtaining accurate information about gastrointestinal (GI) symptoms is critical to achieving the goals of clinical research and practice. The accuracy of patient data is especially important for functional GI disorders (e.g., IBS) whose symptoms lack a biomarker and index illness severity and treatment response.

NIDDK Grantee News

Dec 23, 2014

Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of uncomplicated urinary tract infection (UTI), manifested by inflammation of the urinary bladder, in humans and is a major global public health concern.

NIDDK Grantee News

Dec 22, 2014

The dorsal mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12.

NIDDK Grantee News

Dec 17, 2014

Hypoglycemia initiates the counter-regulatory response (CRR), in which the sympathetic nervous system, glucagon and glucocorticoids restore glucose to appropriate concentrations. During starvation, low leptin levels restrain energy utilization, enhancing long-term survival.

NIDDK Grantee News

Dec 11, 2014

Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD.

NIDDK Grantee News

Dec 11, 2014

Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease.

NIDDK Grantee News

Dec 4, 2014

Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood.

NIDDK Grantee News

Dec 4, 2014

Lysosomal degradation of cytoplasmic components by autophagy is essential for cellular survival and homeostasis under nutrient-deprived conditions. Acute regulation of autophagy by nutrient-sensing kinases is well defined, but longer-term transcriptional regulation is relatively unknown.

NIDDK Grantee News

Dec 4, 2014

Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not.

NIDDK Grantee News

Dec 4, 2014

Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined.

NIDDK Grantee News

Dec 2, 2014

Because current therapeutics for obesity are limited and only offer modest improvements, novel interventions are needed. Preventing obesity with time-restricted feeding (TRF; 8-9 hr food access in the active phase) is promising, yet its therapeutic applicability against preexisting obesity, diverse dietary conditions, and less stringent eating patterns is unknown.

NIDDK Grantee News

Nov 20, 2014

Differentiation of human pluripotent stem cells (hPSCs) into organ-specific subtypes offers an exciting avenue for the study of embryonic development and disease processes, for pharmacologic studies and as a potential resource for therapeutic transplant.

NIDDK Grantee News

Nov 18, 2014

Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding.

NIDDK Grantee News

Nov 6, 2014

Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear.

NIDDK Grantee News

Nov 1, 2014

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry.

NIDDK Grantee News

Oct 24, 2014

The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection.

NIDDK Grantee News

Oct 9, 2014

Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16- to 18-fold in these mice.

NIDDK Grantee News

Oct 2, 2014

Recent studies have associated lower urinary tract symptoms (LUTS) in men with prostatic fibrosis, but a definitive link between collagen deposition and LUTS has yet to be demonstrated.

NIDDK Grantee News

Sep 2, 2014

The increase in the prevalence of diabetes over the past few decades has coincided with an increase in certain risk factors for diabetes, such as a changing race/ethnicity distribution, an aging population, and a rising obesity prevalence.

NIDDK Grantee News

Aug 1, 2014

The HMG-CoA reductase inhibitors (statins) are widely prescribed for patients with hyperlipidemia and are generally well tolerated. Mild elevations in serum aminotransferases arise in up to 3% of treated patients, but clinically apparent drug-induced liver injury is rare. The aim of this study is to report the presenting features and outcomes of 22 patients with clinically apparent liver injury due to statins.