A5061837667- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Neuropeptides and Animal Physiology
- Digestive system and related health
- Metabolism, Diabetes, and Cancer
- Neuroendocrine Tumor Research Advances
- Growth Hormone and Insulin-like Growth Factors
- Regulation of Appetite and Obesity
- Diet, Metabolism, and Disease
- Circadian rhythm and melatonin
- Peptidase Inhibition and Analysis
- Diet and metabolism studies
- Dietary Effects on Health
- Helicobacter pylori-related gastroenterology studies
- Clinical Nutrition and Gastroenterology
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Cancer Cells and Metastasis
- Infant Nutrition and Health
- Biochemical Analysis and Sensing Techniques
- Pancreatic and Hepatic Oncology Research
- Gastrointestinal motility and disorders
- Genetic factors in colorectal cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Gastroesophageal reflux and treatments
University of Toronto
2014-2023
Muscular Dystrophy Canada
2022
Rockefeller University
2020
Brigham and Women's Hospital
2020
Wellcome/MRC Institute of Metabolic Science
2020
University of Cambridge
2020
Wellcome Trust
2020
Mayo Clinic
2020
Federation of American Societies for Experimental Biology
2020
Hospital for Sick Children
2020
Injury, inflammation, or resection of the small intestine results in severe compromise intestinal function. Nevertheless, therapeutic strategies for enhancing growth and repair mucosal epithelium are currently not available. We demonstrate that nude mice bearing subcutaneous proglucagon-producing tumors exhibit marked proliferation epithelium. The factor responsible inducing was identified as glucagon-like peptide 2 (GLP-2), a 33-aa with no previously ascribed biological GLP-2 stimulated...
Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion, suggesting the existence a proximal gut signal regulating GLP-1 release from L cells distal small intestine. Glucose-dependent insulinotropic peptide (GIP) has been shown to be one such signal; however, dependence GIP on gastrin-releasing peptide, neuromodulator, suggested role for nervous system in this proximal-distal loop. Investigations into nature were therefore conducted an situ model rat...
The proglucagon gene (glu) encodes glucagon, expressed in pancreatic islets, and the insulinotropic hormone GLP-1, intestines. These two hormones exert critical opposite effects on blood glucose homeostasis. An intriguing question that remains to be answered is whether how glu expression regulated a cell type-specific manner. We reported previously promoter gut endocrine lines was stimulated by β-catenin, major effector of Wnt signaling pathway, whereas mRNA GLP-1 synthesis were activated...
Intestinal L-cells secrete the incretin glucagon-like peptide-1 (GLP-1) in response to ingestion of nutrients, especially long-chain fatty acids. The Galphas-coupled receptor GPR119 binds acid derivate oleoylethanolamide (OEA), and agonists enhance GLP-1 secretion. We therefore hypothesized that OEA stimulates release through a GPR119-dependent mechanism.Murine (m) GLUTag, human (h) NCI-H716, primary fetal rat intestinal L-cell models were used for RT-PCR cAMP radioimmunoassay. Anesthetized...
Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial proliferation. We studied crypt cell proliferation, enterocyte death, and feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption [7.7 +/- 0.3 vs. 8.0 0.4 g/day, saline (control) mice, P = not significant]; however, increased the proliferation rate (46.0 1 57 5%, control GLP-2, < 0.01) decreased apoptotic (5.9 0.7 2.8 0.2% cells, 0.05) small bowel (SB) epithelium. induced a significant...
Glucagon-like peptide-1(7-36NH2) (GLP-1) and peptide YY(3-36NH2) (PYY(3-36NH2)) are cosecreted from the intestine in response to nutrient ingestion. Peripheral administration of GLP-1 or PYY(3-36NH2) decreases food intake (FI) rodents humans; however, exact mechanisms by which these peptides regulate FI remain unclear. Male C57BL/6 mice were injected (ip) with exendin-4(1-39) (Ex4, a receptor agonist) and/or (0.03-3 microg), was determined for up 24 h. Ex4 alone decreased 83 26%,...
We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. now report second PC1 deficiency B), also due to compound heterozygosity for novel missense nonsense mutations. While both subjects shared phenotypes hypoglycemia, elevated circulating levels certain prohormones, clinical presentation Subject B was dominated by severe refractory neonatal diarrhea,...
We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. now report second PC1 deficiency B), also due to compound heterozygosity for novel missense nonsense mutations. While both subjects shared phenotypes hypoglycemia, elevated circulating levels certain prohormones, clinical presentation Subject B was dominated by severe refractory neonatal diarrhea,...
The gene encoding proglucagon is expressed predominantly in the pancreas and intestine. physiological importance of glucagon secreted from islets Langerhans has engendered considerable interest molecular control transcription endocrine pancreas. In contrast, little known about expression recent demonstration that glucagon-like peptide-1 (GLP-1) intestine a potent regulator insulin secretion glucose homeostasis stimulated renewed factors GLP-1 synthesis intestinal L-cell. To develop model for...
Incretins are intestinal factors that stimulate postprandial insulin secretion in preparation for subsequent rises plasma levels of ingested nutrients. Glucose-dependent insulinotropic peptide (GIP), a duodenal endocrine peptide, is ideally located such function. In contrast, the proglucagon-derived (PGDP), truncated GLP-1 [GLP-1(7-37) or tGLP-1] equipotent to GIP activity, but due its localization distal ileum, appears be poorly situated fulfill an incretin role response direct nutrient...
Glucagon-like peptide-1 (GLP-1), released from intestinal endocrine L cells, is a potent insulinotropic hormone. GLP-1 secretion diminished in obese patients. Because obesity linked to abnormal leptin signaling, we hypothesized that may modulate secretion. Leptin significantly stimulated (by up 250% of control) fetal rat mouse cell line (GLUTag), and human (NCI-H716) dose-dependent manner (P &lt; 0.05–0.001). The long form the receptor was shown be expressed, induced phosphorylation...
Glucagon-like peptide-2 (GLP-2) stimulates small intestinal growth through induction of epithelial proliferation. To examine the physiology GLP-2-induced bowel, mice were treated with GLP-2 (2.5 micrograms) or vehicle for 10 days. Small weight increased to 136 +/- 2% controls in GLP-2-treated mice, parallel 1.4 0.1- and 1.9 0.5-fold increments duodenal RNA protein content, respectively (P < 0.05-0.001). Similarly, activities maltase, sucrase, lactase, glutamyl transpeptidase,...
Glucagon-like peptide-1 (GLP-1) regulates energy intake, gastrointestinal motility, and nutrient disposal. The relative importance of the islet β-cell for GLP-1 actions remains unclear. We determined role pancreatic duodenal homeobox-1 (Pdx1) transcription factor receptor (GLP-1R)-dependent through analysis mice with β-cell–specific inactivation Pdx1 gene (β-cellPdx1−/− mice). GLP-1R agonist exendin-4 (Ex-4) reduced glycemic excursion following intraperitoneal (i.p.) glucose challenge in...
Glucagon-like peptide 1 (GLP-1) is a gut-derived secreted from intestinal L-cells after meal. GLP-1 has numerous physiological actions, including potentiation of glucose-stimulated insulin secretion, enhancement β-cell growth and survival, inhibition glucagon release, gastric emptying, food intake. These antidiabetic effects have led to intense interest in the use this for treatment patients with type 2 diabetes. Oral nutrients such as glucose fat are potent regulators but non-nutrient...
Insulin resistance and type 2 diabetes mellitus are associated with impaired postprandial secretion of glucagon-like peptide-1 (GLP-1), a potent insulinotropic hormone. The direct effects insulin on the L cell unknown. We therefore hypothesized that is responsive to impairs GLP-1 secretion. were examined in well-characterized models: murine GLUTag, human NCI-H716, fetal rat intestinal cells. MKR mice, model chronic hyperinsulinemia, used assess function vivo. In all cells, activated...
The proglucagon gene (glu) encodes the incretin hormone glucagon-like peptide-1 (GLP-1), produced in intestinal endocrine L cells. We found previously that bipartite transcription factor beta-catenin/T cell (cat/TCF), major effector of canonical Wnt signaling pathway, activates glu expression and GLP-1 production. show here 100 nm insulin stimulated enhanced content GLUTag line as well primary fetal rat cultures. Increased mRNA were also observed vivo hyperinsulinemic MKR mice. In cells,...