Reduced glucose uptake precedes insulin signaling defects in adipocytes from heterozygous GLUT4 knockout mice.

Decreased GLUT4 expression, impaired insulin receptor (IR), IRS-1, and pp60/IRS-3 tyrosine phosphorylation are characteristics of adipocytes from insulin-resistant animal models and obese NIDDM humans. However, the sequence of events leading to the development of insulin signaling defects and the significance of decreased GLUT4 expression in causing adipocyte insulin resistance are unknown. The present study used male heterozygous GLUT4 knockout mice (GLUT4(+/-)) as a novel model of diabetes to study the development of insulin signaling defects in adipocytes with the progression of whole body insulin resistance and diabetes.

Beta1,4-galactosyltransferase and lactose biosynthesis: recruitment of a housekeeping gene from the nonmammalian vertebrate gene pool for a mammary gland specific function.

Beta1,4-galactosyltransferase (beta4GalT-I) is a constitutively expressed trans-Golgi enzyme, widely distributed in vertebrates, which synthesizes the beta4-N-acetyllactosamine structure commonly found in glycoconjugates. In mammals beta4GalT-I has been recruited for a second biosynthetic function, the production of lactose; this function takes place exclusively in the lactating mammary gland. In preparation for lactose biosynthesis, beta4GalT-I enzyme levels are increased significantly.

Are 99mTc leukocyte scintigraphy and SBFT studies useful in children suspected of having inflammatory bowel disease?

Objective: The goal of this retrospective study was to assess whether 99mTc-white blood cell (WBC) scintigraphy and upper gastrointestinal small bowel follow-through (UGI-SBFT) could exclude inflammation in children suspected of having inflammatory bowel disease (IBD).

Methods: Of a population of 313 children who had a 99mTc-WBC scan, 130 children were studied exclusively to rule out IBD. Sixty-nine colonoscopies with biopsies were done within a short time interval of the 99mTc-WBC scans.

Amelioration of insulin resistance but not hyperinsulinemia in obese mice overexpressing GLUT4 selectively in skeletal muscle.

The effects of gold-thioglucose (GTG) treatment were examined in mice overexpressing GLUT4 selectively in skeletal muscle (MLC-GLUT4 mice) and in age-matched controls. Groups of MLC-GLUT4 and control mice were injected with GTG or saline at 5 weeks of age. At 12 weeks following the injections, GTG-treated control mice exhibited a 35% increase in body weight versus saline-treated controls.

Postexercise glucose uptake and glycogen synthesis in skeletal muscle from GLUT4-deficient mice.

To determine the role of GLUT4 on postexercise glucose transport and glycogen resynthesis in skeletal muscle, GLUT4-deficient and wild-type mice were studied after a 3 h swim exercise. In wild-type mice, insulin and swimming each increased 2-deoxyglucose uptake by twofold in extensor digitorum longus muscle. In contrast, insulin did not increase 2-deoxyglucose glucose uptake in muscle from GLUT4-null mice.

Predominant expression of the mitochondrial dicarboxylate carrier in white adipose tissue.

We report the identification of a novel mouse protein closely related to the family of mitochondrial uncoupling proteins and the oxoglutarate carrier. The cDNA encodes a protein of 287 amino acids that shares all the hallmark features of the mitochondrial transporter superfamily, including six predicted transmembrane domains. It is nearly identical to the sequence recently reported for the rat mitochondrial dicarboxylate carrier (DIC).

Metabolism of d-glucose and its pentaacetate ester in muscles and pancreatic islets of GLUT4 null mice.

The metabolism of d-glucose and its pentaacetate ester was investigated in GLUT4 null mice and control C57Bl6/CBA mice. The incorporation of d-[U-(14)C]glucose (1.7 mM) into glycogen of diaphragm, soleus, and extensor digitorium longus muscles averaged, in the GLUT4 null mice, only 34 +/- 7% of the mean corresponding control values.

Gastric and small bowel Crohn's disease assessed with leukocytes-Tc(99m) scintigraphy.

We reviewed 312 (99m)Tc leukocyte (99m)Tc-WBC studies to evaluate the sensitivity and specificity of (99m)Tc-WBC for identifying small-bowel and gastric inflammation in children with Crohn's disease. The (99m)Tc-WBC scans were interpreted blindly and compared to the results of colonoscopy with biopsies and surgical specimens. In 46 children, total colonoscopy was done within a few days of a (99m)Tc- WBC scan and in 13 others surgical specimens were available.

In vitro analysis of the glucose-transport system in GLUT4-null skeletal muscle.

We have characterized the glucose-transport system in soleus muscle from female GLUT4-null mice to determine whether GLUT1, 3 or 5 account for insulin-stimulated glucose-transport activity. Insulin increased 2-deoxyglucose uptake 2.8- and 2.

Pediatric inflammatory bowel disease: assessment with scintigraphy with 99mTc white blood cells.

Purpose: To evaluate the sensitivity and specificity of scintigraphy with technetium 99m white blood cells (WBC) for detection of colonic inflammation in children with and children without inflammatory bowel disease (IBD).

Materials And Methods: In 215 patients, uptake of 99mTc WBC in 3,440 bowel segments was graded. In 137 of the 215 patients, the 99mTc WBC scans were interpreted blindly and findings compared with results at colonoscopy and endoscopic biopsy.

A novel 14-base-pair regulatory element is essential for in vivo expression of murine beta4-galactosyltransferase-I in late pachytene spermatocytes and round spermatids.

During murine spermatogenesis, beginning in late pachytene spermatocytes, the beta4-galactosyltransferase-I (beta4GalT-I) gene is transcribed from a male germ cell-specific start site. We had shown previously that a 796-bp genomic fragment that flanks the germ cell start site and contains two putative CRE (cyclic AMP-responsive element)-like motifs directs correct male germ cell expression of the beta-galactosidase reporter gene in late pachytene spermatocytes and round spermatids of transgenic mice (N. L.

Oral versus initial intravenous therapy for urinary tract infections in young febrile children.

Background: The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy.

Methods: In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by 99mTc-dimercaptosuccinic acid renal scans).

Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice.

The mouse ob gene encodes leptin, an adipocyte hormone that regulates body weight and energy expenditure. Leptin has potent metabolic effects on fat and glucose metabolism. A mutation of the ob gene results in mice with severe hereditary obesity and diabetes that can be corrected by treatment with the hormone.

Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle.

Impaired skeletal muscle glucose utilization under insulin action is a major defect in the etiology of type 2 diabetes. This is underscored by a new mouse model of type 2 diabetes generated by genetic disruption of one allele of glucose transporter 4 (GLUT4+/-), the insulin-responsive glucose transporter in muscle and adipose tissue. Male GLUT4+/- mice exhibited decreased GLUT4 expression and glucose uptake in muscle that accompanied impaired whole-body glucose utilization, hyperinsulinemia, hyperglycemia, and heart histopathology.

Assessment of terminal ileal and colonic inflammation in Crohn's disease with 99mTc-WBC.

We evaluated the sensitivity and specificity of Technetium-99m (99mTc)-white blood cell (WBC) for identifying terminal ileum inflammation in children with Crohn's disease (CD). In 40 children, total colonoscopy was done within a few days of a 99mTc-WBC scan carried out to evaluate the inflammation in children with CD. In 38 patients the intensity and the location of inflammation shown on the 99mTc-WBC scan of the colon were similar to the biopsy result of the colonoscopy.

Downregulation of uncoupling protein 2 mRNA in white adipose tissue and uncoupling protein 3 mRNA in skeletal muscle during the early stages of leptin treatment.

The mechanisms underlying the increase in energy expenditure during leptin treatment are not clear. We recently showed that a 5-h intravenous or intracerebroventricular infusion of leptin elevated basal glucose uptake in skeletal muscle (SM) and brown adipose tissue and increased whole-body glucose turnover in C57Bl/6J mice (Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ: Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389:374-377, 1997).

The increased level of beta1,4-galactosyltransferase required for lactose biosynthesis is achieved in part by translational control.

beta1,4-Galactosyltransferase (beta4GalT-I) participates in both glycoconjugate biosynthesis (ubiquitous activity) and lactose biosynthesis (mammary gland-specific activity). In somatic tissues, transcription of the mammalian beta4GalT-I gene results in a 4.1-kb mRNA and a 3.

Unexpected expression of glucose transporter 4 in villous stromal cells of human placenta.

Glucose transporter 4 (GLUT4) protein expression was characterized in human and rodent term placentas. A 50-kDa protein was detected, by immunoblotting, in term human placenta at levels averaging 25% of those found in white adipose tissue. It was also present, albeit at lower levels, in mouse and rat placentas.

Use of technetium-tagged white blood cells in patients with Crohn's disease and ulcerative colitis: is differential diagnosis possible?

Background: Studies have suggested that scans with technetium-tagged white blood cells (WBC-Tc99m) may be equal to endoscopy in the assessment of extent and activity of inflammatory bowel disease (IBD).

Objective: We have retrospectively examined the accuracy of WBC-Tc99m scans in differentiating continuous from discontinuous colitis in pediatric IBD.

Materials And Methods: There were 207 children in the study (96 boys, 111 girls, median age 13 years).

Comparison of the sensitivity of early versus delayed imaging with Tc-99m HMPAO WBC in children with inflammatory bowel disease.

The difference in sensitivity of early imaging at 30 minutes after injection of Tc-99m HMPAO WBC versus delayed imaging at 2 or 3 hours for depiction of active inflammation in children with inflammatory bowel disease was established. The charts of 220 children who had early (30-minute) and delayed (2 or 3 hours) imaging performed for evaluation of inflammatory bowel disease were reviewed. There were 107 boys and 113 girls (average age, 12 years; median, 13 years).

Insulin signaling and glucose transport in insulin resistant skeletal muscle. Special reference to GLUT4 transgenic and GLUT4 knockout mice.

Glucose homeostasis is impaired in patients with non-insulin dependent diabetes mellitus (NIDDM) and this defect in due in part, to defects in glucose transport in skeletal muscle. Intense interest is now focused on whether reduced insulin-mediated glucose transport in muscle from NIDDM patients results from alterations in the insulin signal transduction pathway or from alterations in traffic and/or translocation of GLUT4 to the plasma membrane. Recently, potential targets for impaired traffic/translocation of GLUT4 have been reported to include defective phosphorylation of IRS-1 and reduced PI-3 kinase activity.

Characterization of late abdominal accumulation of 99Tcm-HMPAO leukocytes in a large population of children.

We retrospectively evaluated the incidence of late accumulation of 99Tcm-HMPAO leukocytes (99Tcm-WBC) in the right lower quadrant of a large population of children and characterized some predictive patterns that would enable differentiation of active inflammation from this late occasional accumulation of 99Tcm-WBC. We reviewed the charts of 211 children. The first group evaluated consisted of 79 controls: 30 normal children with no gastrointestinal disease, but who underwent 99Tcm-WBC scanning for other medical problems, and 49 children who had non-specific gastrointestinal (GI) complaints, but had no demonstrable inflammatory bowel disease by conventional diagnostic methods.