A5016294176- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Diabetes and associated disorders
- Diabetes Treatment and Management
- Muscle metabolism and nutrition
- Ruminant Nutrition and Digestive Physiology
- Animal Nutrition and Physiology
- Metabolism and Genetic Disorders
- Adipose Tissue and Metabolism
- Genetic and phenotypic traits in livestock
- Regulation of Appetite and Obesity
- Lipid Membrane Structure and Behavior
- Horticultural and Viticultural Research
- Erythrocyte Function and Pathophysiology
- Plant Physiology and Cultivation Studies
- Crop Yield and Soil Fertility
- Meat and Animal Product Quality
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Hemoglobin structure and function
- Spectroscopy Techniques in Biomedical and Chemical Research
- Neuropeptides and Animal Physiology
Vanderbilt University
2016-2025
Nashville Oncology Associates
2019-2024
Newport (United States)
2019
Institute of Molecular Biology and Biophysics
2017
Zafgen (United States)
2016
Unité Mixte de Recherche sur les Herbivores
2007-2015
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2008
Unité de Nutrition Humaine
2008
Centre de Recherche en Nutrition Humaine d'Auvergne
2008
University of Washington
2004
Abstract Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined understanding role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions from the gut-microbiota, diet, novel endogenous biosynthesis. Investigations included intestinal germ-free study a diet dose response study. Endogenous...
Insulin can inhibit hepatic glucose production (HGP) by acting directly on the liver as well indirectly through effects adipose tissue, pancreas, and brain. While insulin's indirect are indisputable, their physiologic role in suppression of HGP seen response to increased insulin secretion is not clear. Likewise, mechanisms which suppresses lipolysis pancreatic α cell under circumstances also debated. In this study, was infused into portal vein mimic secretion, were blocked either...
The second meal effect describes an improved glycemic response observed after consuming a identical meal. We previously showed that morning (AM) exposure to hyperinsulinemia primes the liver for enhanced hepatic glucose uptake and glycogen storage in afternoon (PM), with no significant on PM non-hepatic uptake. Given meals often trigger both insulin glucagon secretion, we aimed determine if AM hyperglucagonemia alters priming of metabolism. To test this, dogs were exposed 4h...
The importance of hypothalamic insulin action to the regulation hepatic glucose metabolism in presence a normal liver/brain ratio (3:1) is unknown. Thus, we assessed role central response liver physiologic hyperinsulinemia over 4 h. Using pancreatic clamp, portal vein delivery was increased three- or eightfold conscious dog. Insulin studied absence intracerebroventricularly mediated blockade action. Euglycemia maintained, and glucagon clamped at basal. Both molecular metabolic aspects were...
Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, was infused into hepatic Po or a peripheral (Pe) at rate four times of basal. protocol 1, full counterregulatory response allowed, whereas 2, glucagon fixed basal, mimicking diminished α-cell hypoglycemia seen T1DM. glucose fell faster with Pe than insulin,...
Liver glycogen is important for the counterregulation of hypoglycemia and reduced in individuals with type 1 diabetes (T1D). Here, we examined effect varying hepatic content on counterregulatory response to low blood sugar dogs. During first 4 hours each study, was increased by augmenting glucose uptake using hyperglycemia a low-dose intraportal fructose infusion. After levels were increased, animals underwent 2-hour control period no infusion followed hyperinsulinemic/hypoglycemic clamp....
The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic disposition have not been clearly defined. Likewise, molecular defects associated with postprandial hyperglycemia and impaired uptake (HGU) following consumption a high-fat, high-fructose diet (HFFD) are unknown. Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, PoG signaling in normal chow-fed (CTR) HFFD-fed dogs. In CTR dogs, we demonstrated that...
The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In case protein-rich meal, amino acids (AA) stimulate glucagon secretion α-cell. aim present study was to determine impact rise on AA metabolism, particularly liver. We used conscious catheterized dog model recreate condition using pancreatic clamp. Portal infusions glucose, AA, insulin were achieve levels, while portal infusion either maintained at basal level or...
This study assessed the effectiveness of surgical sympathetic denervation common hepatic artery (CHADN) in improving glucose tolerance. CHADN eliminated norepinephrine content liver and partially decreased it pancreas upper gut. We oral tolerance at baseline after 4 weeks high-fat high-fructose (HFHF) feeding. Dogs were then randomized to sham surgery (SHAM) (n = 9) or 11) retested 2.5 3.5 later while still on HFHF diet. improved by ∼60% part because enhanced insulin secretion, as indicated...
In dogs consuming a high-fat and -fructose diet (52 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, portal delivery is markedly blunted with reduction glucokinase (GK) protein glycogen synthase (GS) activity. The present study compared the impact selective increases dietary fat fructose on liver metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric (HFA) high-fructose (HFR) diets wk before undergoing...
We observed that a 4-h morning (AM) duodenal infusion of glucose versus saline doubled hepatic uptake (HGU) and storage during hyperinsulinemic–hyperglycemic (HIHG) clamp afternoon (PM). To separate the effects AM hyperglycemia hyperinsulinemia on PM response, we used balance tracer ([3-3H]glucose) techniques in conscious dogs. From 0 to 240 min, dogs underwent euinsulinemic-hyperglycemic (GLC; n = 7) or hyperinsulinemic-euglycemic (INS; 8) clamp. Tracer equilibration basal sampling occurred...
It has been proposed that brain glucagon action inhibits glucagon-stimulated hepatic glucose production (HGP), which may explain, at least in part, why glucagon's effect on HGP is transient. However, the pharmacologic off-target effects of have responsible for previously observed effects. Therefore, aim this study was to determine if central plays a physiologic role regulation HGP. Insulin maintained baseline while either infused into carotid and vertebral arteries or peripheral (leg) vein...
The purpose of this study was to determine the effect liver glycogen loading on net hepatic synthesis during hyperinsulinemia or portal vein glucose infusion in vivo. Liver levels were supercompensated (SCGly) two groups (using intraportal fructose infusion) but not others (Gly) hyperglycemic-normoinsulinemia. Following a 2-h control period which stopped, there experimental response hyperglycemia plus either 4× basal insulin (INS) (PoG) measured. Increased reduced percent taken up by that...
Glucagon rapidly and profoundly stimulates hepatic glucose production (HGP), but for reasons that are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course of glucagon-mediated molecular events their relevance to metabolic flux in livers conscious dogs. was either infused into hepato-portal vein at sixfold basal rate presence somatostatin insulin, or it maintained level control studies. In one group, remained...
Abstract Aims We previously quantified the hypoglycaemia‐sparing effect of portal vs peripheral human insulin delivery. The current investigation aimed to determine whether a bioequivalent vein infusion hepatopreferential analog, insulin‐406, could similarly protect against hypoglycaemia. Materials and methods Dogs received infusions into either hepatic (PoHI, n = 7) or (PeHI, for 180 minutes at four‐fold basal secretion rate (6.6 pmol/kg/min) in previous study. Insulin‐406 (Pe406, was...
Glucagon’s effect on hepatic glucose production (HGP), under hyperglycemic conditions, is time dependent such that after an initial burst of HGP, it slowly wanes. It not known whether this also the case hypoglycemic where increase in HGP essential. This question was addressed using adrenalectomized dogs to avoid confounding effects other counterregulatory hormones. During study, infusions epinephrine and cortisol were given maintain basal levels. Somatostatin insulin (800 µU·kg −1 ·min )...
We investigated the effect of relative changes in dietary nitrogen (N) and energy supply subsequent variations net portal appearance (NPA) nitrogenous nutrients on amino acid (AA) uptake by liver N to peripheral tissues. Six lambs were catheterised across splanchnic tissues received, a replicated Latin square, one three treatments. The diets formulated either match requirements (C), or only 0.8 requirement (LN) (LE). Net fluxes AA urea-N measured portal-drained viscera, estimation arterial...
It is unknown whether activation of hepato-portal vein (PV) glucose sensors plays a role in incretin hormone amplification oral glucose-stimulated insulin secretion (GSIS). In previous studies, PV infusion increased GSIS through mechanisms, perhaps neural stimulation pancreatic β-cells and/or gut release. Thus, there could be difference the effect when comparing with portal rather than leg (LV) infusion. Plasma and hormones were studied six overnight-fasted dogs. An tolerance test (OGTT) was...
Dogs consuming a hypercaloric high-fat and -fructose diet (52 17% of total energy, respectively) or high in either fructose fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) glycogen deposition response to hyperinsulinemia, hyperglycemia, portal delivery. The effect containing neither nor excessive has not been examined. with an initial weight ≈25 kg consumed chow meat (31% protein, 44% carbohydrate, 26% fat) weight-maintaining (CTR; n = 6) (Hkcal; 7) amounts (cumulative gain...