A5084966112- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Diabetes Management and Research
- Diabetes Treatment and Management
- Diet, Metabolism, and Disease
- Parkinson's Disease Mechanisms and Treatments
- Liver Disease Diagnosis and Treatment
- Fungal and yeast genetics research
- Erythrocyte Function and Pathophysiology
- Adipose Tissue and Metabolism
- Neurotransmitter Receptor Influence on Behavior
- Neuropeptides and Animal Physiology
- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Bariatric Surgery and Outcomes
- Polyamine Metabolism and Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Adenosine and Purinergic Signaling
- Nutrition, Genetics, and Disease
- Biochemical and Molecular Research
- Diet and metabolism studies
- Cannabis and Cannabinoid Research
- Genetic Associations and Epidemiology
AstraZeneca (United States)
2020-2024
AstraZeneca (Brazil)
2024
Regeneron (United States)
2022-2023
Bioscience Research
2021
The University of Texas MD Anderson Cancer Center
2014
La Roche College
2001-2013
The King's College
2010-2011
University of Asmara
2011
Roche (Switzerland)
2000-2010
Grimsby Institute
2009
Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior men of a Dutch family. line transgenic mice was isolated which transgene integration caused deletion the gene encoding MAOA, providing animal model MAOA deficiency. In pup brains, concentrations were increased up ninefold, serotonin-like immunoreactivity present catecholaminergic neurons. adult norepinephrine twofold,...
Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of cells that express this enzyme, such as pancreatic beta and hepatocytes. We describe class antidiabetic agents act nonessential, mixed-type GK activators (GKAs) increase affinity maximum velocity (Vmax) GK. GKAs augment both hepatic metabolism glucose-induced insulin secretion from isolated rodent islets, consistent with expression function cell types. In several models type 2 diabetes...
Aims To characterize the pharmacology of MEDI0382 , a peptide dual agonist glucagon‐like peptide‐1 ( GLP ‐1) and glucagon receptors. Materials methods was evaluated in vitro for its ability to stimulate cAMP accumulation cell lines expressing transfected recombinant or endogenous ‐1 receptors, potentiate glucose‐stimulated insulin secretion GSIS ) pancreatic β‐cell hepatic glucose output HGO by primary hepatocytes. The reduce body weight improve energy balance (i.e. food intake expenditure),...
The limited expandability of subcutaneous adipose tissue, due to reduced ability recruit and differentiate new adipocytes, prevents its buffering effect in obesity is characterized by expanded adipocytes (hypertrophic obesity). Bone morphogenetic protein-4 (BMP4) plays a key role regulating adipogenic precursor cell commitment differentiation. We found BMP4 be induced secreted differentiated (pre)adipocytes, was increased large cells. However, the cells exhibited resistance owing secretion...
The glucose-phosphorylating enzyme glucokinase has structural, kinetic, and molecular genetic features that are ideal for its primary role as glucose sensor in a network of neuro/endocrine sentinel cells maintain homeostasis many vertebrates including humans. glucokinase-containing, insulin-producing β-cells the pancreas take prominent lead this network, functioning aggregate master gland. also conceptualized prototype all other cells, which determines our current understanding...
Monoamine oxidases A and B [MAOA MAOB; amine:oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4] play important roles in the metabolism of neuroactive, vasoactive amines Parkinsonism-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Human MAOA MAOB genes isolated from X chromosome-specific libraries span at least 60 kilobases, consist 15 exons, exhibit identical exon-intron organization. Exon 12 codes for covalent FAD-binding-site is most conserved...
Abstract: Monoamine oxidase (MAO) A and B play important roles in the metabolism of biogenic amines. Northern analysis using 32 P‐labeled subfragments human liver MAO cDNA clones detected a 5‐ 3‐kb transcript, respectively, most tissues examined. However, fetal heart thymus express minute amounts whereas brain, muscle, thymus, spleen, meninges, placenta transcript. Small intestine express, addition to 5‐kb 2‐kb which may arise from an alternative polyadenylation site. transcripts are...
Because nonalcoholic steatohepatitis (NASH) is associated with impaired liver regeneration, we investigated the effects of G49, a dual glucagon‐like peptide‐1/glucagon receptor agonist, on NASH and hepatic regeneration. C57Bl/6 mice fed chow or methionine choline–deficient (MCD) diet for 1 week were divided into 4 groups: control (chow diet), MCD diet, plus M+G49 (MCD G49). Mice high‐fat (HFD) 10 weeks HFD H+G49 (HFD Following 2 groups) 3 treatment partial hepatectomy (PH) was performed, all...
Monoamine oxidase A and B (MAO B) play important roles in the metabolism of biogenic dietary amines are encoded by two genes derived from a common ancestral gene. The promoter regions for human MAO have been characterized using series 5' flanking sequences linked to growth hormone reporter When these constructs were transfected into NIH3T3, SHSY-5Y, COS7 cells, maximal activity was found 0.14 kilobase (kb) PvuII/DraII fragment (A0.14) 0.15 kb PstI/NaeI (B0.15) B. Both fragments GC-rich,...
OBJECTIVE Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable hyperinsulinism in a limited number families. We report three children with de novo who displayed spectrum clinical phenotypes corresponding marked differences enzyme kinetics. RESEARCH DESIGN AND METHODS Mutations were directly sequenced, and mutants expressed as glutathionyl S-transferase–glucokinase fusion proteins. Kinetic analysis the enzymes included determinations...
Type 2 diabetes is characterized by elevated blood glucose levels resulting from a pancreatic β-cell secretory insufficiency combined with insulin resistance, most significantly manifested in skeletal muscle and liver (1). If untreated, diabetic complications develop that cause loss of vision, peripheral neuropathy, impaired kidney function, heart disease, stroke. The disease has polygenic basis because numerous genes (the latest count exceeding 20) participate its pathogenesis, but modern...
It was reported previously that isolated human islets from individuals with type 2 diabetes mellitus (T2DM) show reduced glucose-stimulated insulin release. To assess the possibility impaired bioenergetics may contribute to this defect, respiration (Vo(2)), glucose usage and oxidation, intracellular Ca(2+), secretion (IS) were measured in pancreatic three healthy diabetic organ donors. Isolated mouse rat studied for comparison. Islets exposed a "staircase" stimulus, whereas IR Vo(2)...
Glucokinase (GK) activation as a potential strategy to treat type 2 diabetes (T2D) is well recognized. Compound 1, glucokinase activator (GKA) lead that we have previously disclosed, caused reversible hepatic lipidosis in repeat-dose toxicology studies. We hypothesized the was due structure-based toxicity and later established it formation of thiourea metabolite, 2. Subsequent SAR studies 1 led identification pyrazine-based analogue 3, lacking thiazole moiety. In vivo metabolite studies,...
Abstract Peptide therapeutics are increasingly used in the treatment of disease, but their administration by injection reduces patient compliance and convenience, especially for chronic diseases. Thus, oral a peptide therapeutic represents significant advance medicine, is challenged gastrointestinal instability ineffective uptake into circulation. Here, we have glucagon-like peptide-1 (GLP-1) as model treating obesity-linked type 2 diabetes, common disease. We describe comprehensive...
Abstract Background Sarcopenia is defined as age-related low muscle mass and function, can also describe the loss of in certain medical conditions, such sarcopenic obesity. Sarcopenic obesity describes function obese individuals; however, sarcopenia an condition occur any age group, a more accurate term with lean (OLLMM). Given limited data on OLLMM (particularly those aged < 65 years), purpose this study was to estimate prevalence adults ≥ 20 years USA. Methods Data from National Health...
The glucokinase regulatory protein (GKRP) inhibits competitively with respect to glucose by forming a protein-protein complex this enzyme. physiological role of GKRP in controlling hepatic activity was addressed using gene targeting disrupt expression. Heterozygote and homozygote knockout mice have substantial decrease expression enzymatic as measured at saturating concentrations when compared wild-type mice, no change basal blood levels. Interestingly, assayed under conditions promote the...
Hepatic glucokinase (GK) moves between the nucleus and cytoplasm in response to metabolic alterations. Here, using heterologous cell systems, we have found that at least two different mechanisms are involved intracellular movement of GK. In absence GK regulatory protein (GKRP) resides only cytoplasm. However, presence GKRP, there association with this until changes milieu prompt its release. does not contain a nuclear localization signal sequence enter GKRP-independent manner because cells...