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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.

NIDDK News Item

Jul 31, 2014

NIH leaders have announced a new collaborative initiative to improve human health by exploring poorly understood genes that have the potential to be modified by medicines.

NIDDK News Item

Jul 8, 2014

Adults with extreme obesity have increased risks of dying at a young age from cancer and many other causes including heart disease, stroke, diabetes, and kidney and liver diseases, according to results of an analysis of data pooled from 20 large studies of people from three countries. The study, led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, found that people with class III (or extreme) obesity had a dramatic reduction in life expectancy compared with people of normal weight. The findings appeared July 8, 2014, in PLOS Medicine.

NIDDK Grantee News

Jul 3, 2014

The presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).

NIDDK News Item

Jul 3, 2014

Acute kidney injury (AKI) and chronic kidney disease (CKD) are closely intertwined, with each disease a risk factor for developing the other and sharing other risk factors in common, as well as sharing causes for the diseases to get worse, and outcomes, suggests a comprehensive analysis by scientists at the National Institutes of Health and George Washington University Medical Center, Washington, D.C. Findings were published July 3 in the New England Journal of Medicine.

NIDDK News Item

Jul 2, 2014

More than one quarter of children with two copies of a high-risk variant in a specific group of genes develop an early sign of celiac disease called celiac disease autoimmunity (CDA) by age 5. The findings are from The Environmental Determinants of Diabetes in Youth consortium, or TEDDY . The National Institutes of Health-funded study, published July 2 in the New England Journal of Medicine , also found that participants in Sweden had higher rates of celiac disease than participants in the United States, Finland and Germany, even with the same genetic risks.

NIDDK Grantee News

Jul 1, 2014

miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance.

NIDDK Grantee News

Jul 1, 2014

Microvillus inclusion disease (MVID) is a severe form of congenital diarrhea that arises from inactivating mutations in the gene encoding myosin Vb (MYO5B). We have examined the association of mutations in MYO5B and disruption of microvillar assembly and polarity in enterocytes. Stable MYO5B knockdown (MYO5B-KD) in CaCo2-BBE cells elicited loss of microvilli, alterations in junctional claudins, and disruption of apical and basolateral trafficking; however, no microvillus inclusions were observed in MYO5B-KD cells.

NIDDK News Item

Jul 1, 2014

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.

NIDDK News Item

Jun 30, 2014

Researchers have developed a new supercooling technique to increase the amount of time human organs could remain viable outside the body. This study was conducted in rats, and if it succeeds in humans, it would enable a world-wide allocation of donor organs, saving more lives.

NIDDK Grantee News

Jun 19, 2014

Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancreas-specific deletion of Clec16a have abnormal mitochondria with reduced oxygen consumption and ATP concentration, both of which are required for normal β cell function.

NIDDK Grantee News

Jun 17, 2014

α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2.

NIDDK News Item

Jun 15, 2014

People with type 1 diabetes who used a bionic pancreas instead of manually monitoring glucose using fingerstick tests and delivering insulin using a pump were more likely to have blood glucose levels consistently within the normal range, with fewer dangerous lows or highs. The full report of the findings, funded by the National Institutes of Health, can be found online June 15 in the New England Journal of Medicine.

NIDDK Grantee News

Jun 15, 2014

The safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions.

NIDDK News Item

Jun 10, 2014

More than 29 million people in the United States have diabetes, up from the previous estimate of 26 million in 2010, according to a report released today by the Centers for Disease Control and Prevention. One in four people with diabetes doesn’t know he or she has it.

NIDDK Grantee News

Jun 5, 2014

Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines.

NIDDK Grantee News

Jun 5, 2014

Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13, and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat.

NIDDK Grantee News

Jun 5, 2014

Subcutaneous white adipose tissue can be induced to undergo “browning” and acquire thermogenic capacity in response to physiological stimuli such as cold exposure or exercise. In this issue of Cell, Qiu et al. and Rao et al. demonstrate that pink-staining eosinophils and alternatively activated macrophages play key roles in an immune cascade mediating this metabolic switch.

NIDDK Grantee News

Jun 4, 2014

Emerging data support bariatric surgery as a therapeutic strategy for management of type 2 diabetes mellitus.

NIDDK Grantee News

Jun 4, 2014

The SEARCH study demonstrated a significant increase in the incidence of type 1 diabetes (T1D) among non–Hispanic white (NHW) youth from 2002 through 2009 overall and in all but the youngest age group. Continued surveillance of T1D in youth in the United States to identify future trends in T1D incidence and to plan for health care delivery is warranted.

NIDDK Grantee News

May 28, 2014

Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy.

NIDDK Grantee News

May 21, 2014

Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia1, 2. For over half a century, this agent has been prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown.

NIDDK Grantee News

May 21, 2014

Lipolysis regulates energy homeostasis through the hydrolysis of intracellular triglycerides and the release of fatty acids for use as energy substrates or lipid mediators in cellular processes. Genes encoding proteins that regulate energy homeostasis through lipolysis are thus likely to play an important role in determining susceptibility to metabolic disorders.

NIDDK Grantee News

May 7, 2014

Despite concern about an “epidemic,” there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups.

NIDDK Grantee News

May 6, 2014

WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade, leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase.

NIDDK Grantee News

May 6, 2014

Men with sickle cell disease (SCD) risk developing priapism. Recognizing that SCD is a disease of hypoxia, we investigated the effect of hypoxia on gene expression in corporal smooth muscle (CSM) cells. Rat CSM cells in vitro were treated with CoCl2 or low oxygen tension to mimic hypoxia. Hypoxic conditions increased expression of genes previously associated with priapism in animal models.

NIDDK Grantee News

May 4, 2014

Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem1, 2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth.

NIDDK News Item

May 4, 2014

Long-term use of a drug combination reduces the risk of recurrent urinary tract infection by up to 80 percent in children with the urinary condition vesicoureteral compared to placebo, according to research funded by the National Institutes of Health. Results were published online May 4 in theNew England Journal of Medicine External Web Site Policy to coincide with presentation at the Pediatric Academic Societies Annual Meeting in Vancouver, British Columbia.

NIDDK News Item

May 3, 2014

Infants with biliary atresia — a rare liver disease — did not benefit from corticosteroid treatment after bile duct surgery and could face more harm, according to a study funded by the National Institutes of Health. Results were published online May 3 in the Journal of the American Medical Association to coincide with the Pediatric Academic Societies annual meeting.

NIDDK Grantee News

May 1, 2014

To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes.

NIDDK Grantee News

May 1, 2014

To investigate the cell-intrinsic aging mechanisms that erode the function of somatic stem cells during aging, we have conducted a comprehensive integrated genomic analysis of young and aged cells. We profiled the transcriptome, DNA methylome, and histone modifications of young and old murine hematopoietic stem cells (HSCs).

NIDDK Grantee News

Apr 15, 2014

Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.

NIDDK Grantee News

Apr 1, 2014

The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered “lipid sensing” by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPARγ expression was reduced by high-fat-diet feeding. Deletion of PPARγ in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate.

NIDDK Grantee News

Mar 20, 2014

Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover.

NIDDK News Item

Mar 13, 2014

In recognition of World Kidney Day 2014 on March 13, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute on Aging (NIA) at the National Institutes of Health remind older Americans about the importance of protecting their kidneys and urge them to better understand the decline of kidney function as people age.

NIDDK Grantee News

Feb 14, 2014

Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.

NIDDK News Item

Feb 4, 2014

The National Institutes of Health, 10 biopharmaceutical companies and several nonprofit organizations today launched an unprecedented partnership to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development.

NIDDK Grantee News

Jan 30, 2014

Reprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in a nonstochastic manner. Subsets of murine hematopoietic progenitors are privileged whose progeny cells predominantly adopt the pluripotent fate with activation of endogenous Oct4 locus after four to five divisions in reprogramming conditions.

NIDDK Grantee News

Jan 28, 2014

The purpose of this study was to determine the effect of tibial nerve stimulation (TNS) on the micturition reflex. Experiments were conducted in 24 rats under urethane anesthesia.

NIDDK Grantee News

Jan 16, 2014

Coevolution of beneficial microorganisms with the mammalian intestine fundamentally shapes mammalian physiology. Here, we report that the intestinal microbe Bacteroides fragilis modifies the homeostasis of host invariant natural killer T (iNKT) cells by supplementing the host’s endogenous lipid antigen milieu with unique inhibitory sphingolipids. The process occurs early in life and effectively impedes iNKT cell proliferation during neonatal development.