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NIDDK Grantee News

Apr 5, 2016

[University of Texas; Medical University of South Carolina] Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction without prior advanced liver disease that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively.

NIDDK Grantee News

Apr 1, 2016

[University of Washington; Indiana University] Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones.

NIDDK Grantee News

Mar 1, 2016

[Harvard Medical School] The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.

NIDDK Grantee News

Feb 25, 2016

[Washington University] Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants.

NIDDK Grantee News

Feb 19, 2016

[Washington University] As we come to appreciate how our microbial communities (microbiota) assemble following birth, there is an opportunity to determine how this facet of our developmental biology relates to the healthy or impaired growth of infants and children. Childhood undernutrition is a devastating global health problem whose long-term sequelae, including stunting, neurodevelopmental abnormalities, and immune dysfunction, remain largely refractory to current therapeutic interventions.

NIDDK Grantee News

Feb 15, 2016

Nephron endowment is determined by the self-renewal and induction of a nephron progenitor pool established at the onset of kidney development. In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors. Transient Six1 activity prefigures, and is essential for, active nephrogenesis.

NIDDK Grantee News

Feb 12, 2016

[University of Colorado] T cell–mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown.

NIDDK Grantee News

Feb 9, 2016

[Baylor College of Medicine] To evaluate mini-dose glucagon in adults with type 1 diabetes using a stable, liquid, ready-to-use preparation. Research Design and Methods Twelve adults with type 1 diabetes receiving treatment with insulin pumps received subcutaneous doses of 75, 150, and 300 μg of nonaqueous glucagon.

NIDDK Grantee News

Feb 1, 2016

[Johns Hopkins University; Yale University] Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide and have been linked to acute interstitial nephritis. Less is known about the association between PPI use and chronic kidney disease (CKD).

NIDDK Grantee News

Jan 29, 2016

[University of Iowa] Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid.

NIDDK Grantee News

Jan 25, 2016

[Massachusetts Institute of Technology; Harvard University] The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue.

NIDDK Grantee News

Jan 25, 2016

[Massachusetts Institute of Technology] The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate.

NIDDK Grantee News

Jan 21, 2016

[International Consortium of a large number of universities] Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals.

NIDDK Grantee News

Jan 15, 2016

[Harvard Medical School] Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia.

NIDDK Grantee News

Jan 15, 2016

[Columbia University; California Institute of Technology] Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA–linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood.

NIDDK Grantee News

Jan 14, 2016

[University of Cincinnati; University of Pittsburgh; Baylor College of Medicine; University of Buffalo; University of Alabama] Severe obesity affects 4.4 million children and adolescents in the United States, and few effective treatments are available. Particular concern has centered on health problems among severely obese adolescents and possible treatment with bariatric surgery.

NIDDK Grantee News

Jan 13, 2016

[Stanford University; Harvard University] The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization.

NIDDK Grantee News

Jan 9, 2016

[University of Montreal] Crohn’s disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn’s disease and ulcerative colitis.

NIDDK Grantee News

Jan 6, 2016

[University of Cambridge, UK] To evaluate feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions without remote monitoring or supervision.

NIDDK Grantee News

Jan 1, 2016

[Harvard Medical School] Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells.

NIDDK Grantee News

Dec 29, 2015

[University of Iowa] Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin—a peptide with high homology to natriuretic peptides (NP)—as an exercise-responsive myokine that acts to enhance exercise capacity in mice.

NIDDK Grantee News

Dec 17, 2015

[University of Southern California; University of California, Los Angeles] Early life stress (ELS) is a risk factor for developing functional gastrointestinal disorders, and has been proposed to be related to a central amplification of sensory input and resultant visceral hyperalgesia. We sought to characterize ELS-related changes in functional brain responses during acute noxious visceral stimulation.

NIDDK Grantee News

Dec 1, 2015

[University of Colorado; George Washington University; University of Oklahoma] To determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy. Research Design and Methods Today was a randomized clinical trial of adolescents with type 2 diabetes.

NIDDK Grantee News

Nov 11, 2015

[Yale University] Kidney transplantation is often the most effective therapy for end-stage renal disease, but there are not enough donor organs to meet the rising demand. Tissue engineering of kidneys is a potential solution to this organ shortage. Achieving microvascular perfusion has been a major barrier to engineering tissues beyond thin muscularized sheets such as the bladder wall.

NIDDK Grantee News

Nov 3, 2015

[University of California, Los Angeles] A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon.

NIDDK Grantee News

Nov 3, 2015

A diurnal rhythm of eating-fasting promotes health, but the eating pattern of humans is rarely assessed. Using a mobile app, we monitored ingestion events in healthy adults with no shift-work for several days. Most subjects ate frequently and erratically throughout wakeful hours, and overnight fasting duration paralleled time in bed.

NIDDK Grantee News

Nov 1, 2015

[University of California, Berkeley; École Polytechnique Fédérale de Lausanne, Switzerland] Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis.

NIDDK Grantee News

Oct 14, 2015

[University of Pennsylvania] Abnormal composition of intestinal bacteria—“dysbiosis”—is characteristic of Crohn’s disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined.

NIDDK Grantee News

Oct 13, 2015

[University of California, Los Angeles] Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively.

NIDDK Grantee News

Sep 16, 2015

[Harvard Medial School] Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression.

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 20, 2015

[University of Groningen, Netherlands; Harvard Medical School] Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time.

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.