Publications by authors named "Leslie Carter"

Aims/hypothesis: Mitochondria are important regulators of the metabolic phenotype in type 2 diabetes. A key factor in mitochondrial physiology is the H-ATP synthase. The expression and activity of its physiological inhibitor, ATPase inhibitory factor 1 (IF1), controls tissue homeostasis, metabolic reprogramming and signalling.

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Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted.

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Objective: To describe the surgical technique and report outcome of dogs undergoing bioprosthesis valve replacement for severe tricuspid regurgitation (TR) secondary to congenital tricuspid valve dysplasia (TVD).

Animals, Materials And Methods: Twelve client-owned dogs (19-43 kg) with TVD underwent tricuspid valve replacement with a bovine pericardial or porcine aortic bioprosthesis with the aid of cardiopulmonary bypass. Anticoagulation with warfarin was maintained for 3 months after surgery and then discontinued.

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An association between glycogen synthase kinase-3 (GSK3) in skeletal muscle and insulin resistance has been demonstrated in type 2 diabetic patients. In addition, inhibition of GSK3 improves insulin action. The aim of the present study was to elucidate the role of the alpha-isoform of GSK3 in insulin resistance in human skeletal muscle cells from nondiabetic subjects maintained in culture.

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The effects of specific emotional states on a laboratory pain task were tested by examining the behavioural, verbal and psychophysiological responses of 80 student volunteers (50% female). Participants were assigned to one of four Velten-style emotion-induction conditions (ie, anxiety, depression, elation or neutral). The sexes of experimenters were counterbalanced.

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Context: The insulin analog LysB3,GluB29-insulin (glulisine) displays accelerated in vivo bioavailability compared with native insulin.

Objective: Biological properties of this rapid-acting insulin analog were compared with the actions of native insulin and IGF-I.

Design: The effects of the hormones on hormone binding, glucose uptake, and thymidine uptake were evaluated in cultured human skeletal muscle cells.

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The impact of type 2 diabetes on the ability of muscle to accumulate and dispose of fatty acids and triglycerides was evaluated in cultured muscle cells from nondiabetic (ND) and type 2 diabetic (T2D) subjects. In the presence of 5 microM palmitate, T2D muscle cells accumulated less lipid than ND cells (11.5 +/- 1.

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We examined the regulation of free fatty acid (FFA, palmitate) uptake into skeletal muscle cells of nondiabetic and type 2 diabetic subjects. Palmitate uptake included a protein-mediated component that was inhibited by phloretin. The protein-mediated component of uptake in muscle cells from type 2 diabetic subjects (78 +/- 13 nmol.

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The relationship between insulin action and control of the adipocyte-derived factor adiponectin was studied in age- and weight-matched obese individuals with type 2 diabetes failing sulfonylurea therapy. After initial metabolic characterization, subjects were randomized to troglitazone or metformin treatment groups; all subjects received glyburide (10 mg BID) as well. Treatment was continued for 3 months.

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The metabolic actions of insulin and insulin-like growth factor-1 (IGF-1) were compared in cultured skeletal muscle cells from nondiabetic (ND) and type 2 diabetic subjects. Insulin stimulated glucose uptake with comparable sensitivity in ND (EC(50) = 2.0 +/- 0.

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Glycogen synthase kinase (GSK)-3 has been implicated in the regulation of multiple cellular physiological processes in skeletal muscle. Selective cell-permeable reversible inhibitors (INHs) of GSK-3 (CT98014 and CHIR98023 [Chiron, Emeryville, CA] and LiCl) were used to evaluate the role of GSK-3 in controlling glucose metabolism. Acute treatment (30 min) of cultured human skeletal muscle cells with either INH resulted in a dose-dependent activation of glycogen synthase (GS) with a maximally effective concentration of approximately 2 micromol/l.

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Free fatty acid (FFA) oxidation in human skeletal muscle cells can be stimulated, both independently and in a synergistic manner, by agonists for PPARgamma and RXR. Increased FFA disposal in muscle through augmented oxidation could reduce intramyocellular lipid accumulation. The abilities of such agents to improve glucose tolerance and insulin action may thus involve effects on both glucose and FFA metabolism.

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