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NIDDK Grantee News

May 17, 2017

[Northwestern University; University of Pittsburgh] Researchers conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors, examining mental well-being, psychological growth, motivations and emotions about their donations. Careful screening may optimize outcomes for potentially vulnerable donors.

NIDDK Grantee News

May 3, 2017

[Texas A&M University Health Science Center] Researchers worked with rat models to demonstrate that renal immune cell infiltration and inflammation cause lymphangiogenesis in hypertension- and aging-associated renal injury.

NIDDK Grantee News

Mar 9, 2017

[Harvard Medical School; University of Osnabrück] Cytokines are classically thought to stimulate downstream signaling pathways through monotonic activation of receptors. We describe a severe anemia resulting from a homozygous mutation (R150Q) in the cytokine erythropoietin (EPO). Study results demonstrate how variation in a single cytokine can lead to biased downstream signaling and can thereby cause human disease. Moreover, researchers have defined a distinct treatable form of anemia through mutation identification and functional studies.

NIDDK Grantee News

Feb 28, 2017

[Colorado School of Public Health; Wake Forest School of Medicine] The increased prevalence of type 2 diabetes among children and adolescents has been relatively recent in most populations, beginning in the early- to mid-1990s. Additionally, a long-term increase in type 1 diabetes has been observed both worldwide and in the United States. These recent epidemiologic trends in type 1 and type 2 diabetes diagnosed in young individuals raise the question of whether the pattern of complications differs by diabetes type at similar ages and diabetes duration. Recent studies have reported a higher prevalence of some but not all complications in children and adolescents with type 2 diabetes compared with those with type 1.

NIDDK Grantee News

Feb 23, 2017

[Joslin Diabetes Center and Harvard Medical School; University of Campinas] Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Transplantation of both white and brown adipose tissue—brown especially—into mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21.

NIDDK Grantee News

Feb 1, 2017

[University of California at San Diego School of Medicine] The aim of this study is to determine the mechanism by which antimuscarinic compounds enhance neurite outgrowth and to translate findings into a therapeutic approach that could prevent or reverse peripheral neuropathy in a range of in vitro and in vivo models. Our data introduce selective or specific antimuscarinic drugs as a therapeutic approach for preventing and reversing sensory neuropathy in a variety of disease states of the PNS.

NIDDK Grantee News

Jan 26, 2017

[University of California, San Francisco; Massachusetts Institute of Technology] Researchers show that an approach combining bioinformatics, synthetic biology, and heterologous gene cluster expression can rapidly expand our knowledge of the metabolic potential of the microbiota while avoiding the challenges of cultivating fastidious commensals.

NIDDK Grantee News

Jan 19, 2017

[Scripps Research Institute; Ecole Polytechnique Federale de Lausanne] Advances have accelerated the discovery of chemical probes for studying biological processes. Researchers here describe a platform that marries fragment-based ligand discovery with quantitative chemical proteomics to map thousands of reversible small molecule-protein interactions directly in human cells. Researchers further explored fragment-based ligands that promote adipogenesis.

NIDDK Grantee News

Jan 12, 2017

[Université of Côte d'Azur] In this study we report the identification of GABA as an inducer of α- to-β-like cell conversion in vivo. Importantly, these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo.

NIDDK Grantee News

Jan 12, 2017

[CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; Université of Côte d'Azur] Generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. Our results in zebrafish, rodents, and primary human pancreatic islets identify gephyrin as a druggable target for the regeneration of pancreatic β cell mass from α cells.

NIDDK Grantee News

Jan 12, 2017

[Harvard Medical School] GABA and the antimalarial drug artemether, which acts on GABAergic pathways, can drive pancreatic cells with an α-cell phenotype toward a β-cell-like phenotype. These drugs can stimulate the production of sufficient numbers of new β-like cells to reverse severe diabetes in mice.

NIDDK Grantee News

Jan 11, 2017

[Washington University School of Medicine] Researchers identified dietary practice (DP)-associated gut bacterial taxa in individuals practicing calorie restriction. When transplanted into mice, the bacterial taxa were linked to enhanced responses to a diet intervention and changes in several metabolic features.

NIDDK Grantee News

Jan 3, 2017

[Columbia University; University of Florida College of Medicine Gainesville] Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Using mice, our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency.

NIDDK Grantee News

Dec 21, 2016

[University of Iowa] Researchers used a transgenic autoimmune cystitis mouse model (URO-OVA) to study pelvic pain. Results provide direct evidence for the role of mast cells in cystitis-associated LUTD (lower urinary tract dysfunction), supporting the use of mast cell inhibitors for treatment of certain forms of interstitial cystitis/bladder pain syndrome.

NIDDK Grantee News

Dec 20, 2016

[Duke University; University of North Carolina at Chapel Hill] Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cystitis, mast cells trigger bladder epithelial cell (BEC) exfoliation during E. coli infection.

NIDDK Grantee News

Dec 19, 2016

[Wellcome Trust Sanger Institute; Mayo Clinic College of Medicine] In this large genome-wide association study of primary sclerosing cholangitis (PSC) researchers identified four new genome-wide significant loci.

NIDDK Grantee News

Dec 5, 2016

[Brigham and Women's Hospital and Harvard Medical School; Boston University School of Public Health] The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat.

NIDDK Grantee News

Nov 23, 2016

[Washington University School of Medicine] Researchers introduced collections of sequenced gut bacterial strains cultured from healthy or underweight Bangladeshi children into germfree mice-fed diets resembling those consumed by the children. Young mouse recipients of undernourished donors’ microbiota exhibit growth faltering, manifested in part by a reduced rate of lean body mass gain compared to recipients of healthy donors’ microbiota. These differences are not associated with differences in food consumption. Adult mouse recipients of undernourished donor’s microbiota exhibit a weight loss (wasting) phenotype.

NIDDK Grantee News

Nov 22, 2016

[University of Michigan Medical School] Study authors have pioneered a strategy using small iron-chelating compounds called siderophores as vaccine antigens. This report highlights the untapped resource of bacteria-specific small molecules as potential vaccine antigens and provides a proof of principle for incorporating these compounds into multicomponent vaccines for the prevention of bacterial infections.

NIDDK Grantee News

Nov 14, 2016

[Oregon State University; University of São Paulo] Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolerance.

NIDDK Grantee News

Nov 10, 2016

[University of Pittsburgh; Northwestern University] Social relationship and financial outcomes were prospectively surveyed before donation and at 3, 6, 12, and 24 months after donation for 271 living liver donors. Relationship changes were positive overall across postdonation time points. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors.

NIDDK Grantee News

Nov 10, 2016

[Washington University School of Medicine] Dietary fat promotes pathological insulin resistance through chronic inflammation. Working in mice, researchers explore how endogenous fat in macrophages is necessary for the development of exogenous fat-induced insulin resistance.

NIDDK Grantee News

Nov 3, 2016

[Chinese Academy of Medical Sciences; University of California San Diego School of Medicine] In obesity, macrophages and other immune cells accumulate in insulin target tissues, promoting a chronic inflammatory state and insulin resistance. Working with mice, researchers administered Galectin-3 (Gal3), a lectin mainly secreted by macrophages, causing insulin resistance and glucose intolerance. In contrast, inhibition of Gal3, through either genetic or pharmacologic loss of function, improved insulin sensitivity in obese mice.

NIDDK Grantee News

Oct 14, 2016

[Johns Hopkins University School of Medicine; Sorbonne Universités] Researchers describe a novel role for an olfactory receptor (OR), Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels.

NIDDK Grantee News

Oct 13, 2016

[Albert Einstein College of Medicine; Harvard Medical School] A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. Here researchers identify mitophagy as a key mechanism of HSC expansion, and suggest potential methods of cell fate manipulation through metabolic pathways.

NIDDK Grantee News

Oct 12, 2016

[Washington University School of Medicine] Uropathogenic E. coli (UPEC) is the dominant cause of urinary tract infections, clinically described as cystitis. Working with a mouse model, researchers identified the role of the F9/Yde/Fml pilus for UPEC persistence in the inflamed urothelium. Vaccination with FmlH significantly protected mice from chronic cystitis.

NIDDK Grantee News

Oct 1, 2016

[Icahn School of Medicine at Mt. Sinai; Yale University] In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony–stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.

NIDDK Grantee News

Oct 1, 2016

[Cedars-Sinai Medical Center; Cleveland Clinic] Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn’s disease (CD) and ulcerative colitis remain incompletely defined. Study results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.

NIDDK Grantee News

Aug 1, 2016

[Medical College of Wisconsin; Case Western Reserve University] Researchers tested whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain. Some chronic pelvic pain types showed autonomic neuropathy and some show vagal withdrawal.

NIDDK Grantee News

Jul 11, 2016

[Oregon Health and Science University; University of Pennsylvania School of Medicine] Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population.

NIDDK Grantee News

Jun 15, 2016

[New York University Langone Medical Center] The intestinal “microbiota,” that is, the community of microbes inhabiting the human intestinal tract, undergoes many changes during the first 2 years of life. Bokulich et al. now show that this pattern of development is altered in children who are delivered by cesarean section, fed formula, or treated with antibiotics, compared to those babies who were born vaginally, breast-fed, or unexposed to antibiotics.

NIDDK Grantee News

Jun 8, 2016

[Yale University School of Medicine] Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae.

NIDDK Grantee News

Jun 7, 2016

[Colorado School of Public Health; University of Colorado School of Medicine] Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass [%FM]) at birth by increasing the FM component of neonatal body composition.

NIDDK Grantee News

Jun 7, 2016

[The Broad Institute of MIT and Harvard; Monash University] Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function.

NIDDK Grantee News

Jun 7, 2016

[University of California San Diego] p62 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored.

NIDDK Grantee News

Jun 1, 2016

[Nationwide Children’s Hospital; University of New South Wales; Medical College of Wisconsin] Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. Kumar et al examined a multinational cross-sectional study of children for risk factors, abdominal pain, and disease burden associated with ARP and CP in childhood.

NIDDK Grantee News

May 27, 2016

[California Institute of Technology] Inflammatory bowel disease (IBD) is associated with risk variants in the human genome and dysbiosis of the gut microbiome, though unifying principles for these findings remain largely undescribed. The human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles (OMVs).

NIDDK Grantee News

May 23, 2016

[Vanderbilt University Medical Center] Basement membranes are defining features of the cellular microenvironment; however, little is known regarding their assembly outside cells. We report that extracellular Cl− ions signal the assembly of collagen IV networks outside cells by triggering a conformational switch within collagen IV noncollagenous 1 (NC1) domains.

NIDDK Grantee News

May 10, 2016

[Washington University School of Medicine; Harvard University; Case Western Reserve University School of Medicine] We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past.

NIDDK Grantee News

May 2, 2016

[National Institute of Diabetes and Digestive and Kidney Diseases] Researchers measured long-term changes in resting metabolic rate (RMR) and body composition in participants of “The Biggest Loser” competition. Body composition was measured by dual energy X-ray absorptiometry, and RMR was determined by indirect calorimetry at baseline, at the end of the 30-week competition and 6 years later.

NIDDK Grantee News

Apr 28, 2016

[University of California San Francisco] Haematopoietic stem cells (HSCs) maintain lifelong blood production and increase blood cell numbers in response to chronic and acute injury. However, the mechanism(s) by which inflammatory insults are communicated to HSCs and their consequences for HSC activity remain largely unknown.

NIDDK Grantee News

Apr 27, 2016

[National Institute of Diabetes and Digestive and Kidney Diseases; University of Murcia, Murcia, Spain] The zona pellucida, a matrix that surrounds ovulated eggs, is the site of sperm recognition and binding, which precede sperm penetration and fertilization. Avella et al. identified a peptide from the zona pellucida called ZP2, which the authors attached to agarose beads to facilitate infertility treatment or, conversely, contraception.

NIDDK Grantee News

Apr 21, 2016

[Baylor College of Medicine] Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin.

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 18, 2016

[Johns Hopkins University School of Medicine; National Institute on Drug Abuse] Overeating and obesity are rapidly becoming worldwide problems. Normally, mice do not overeat—they balance their caloric intake with their caloric needs. Lagerlöf et al. deleted an enzyme called O-GlcNAc transferase (OGT) from a subset of neurons in the mouse hypothalamus (see the Perspective by Schwartz). After the loss of OGT, the animals began to overeat and rapidly gained weight.

NIDDK Grantee News

Mar 10, 2016

[Johns Hopkins University School of Medicine] This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors.

NIDDK Grantee News

Mar 7, 2016

[University of Pennsylvania; Harvard Medical School] Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear. Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species, a process that requires blood-borne lipids to initially traverse the blood vessel wall.

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.