A5035694463- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Diabetes Management and Research
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Liver Disease Diagnosis and Treatment
- Regulation of Appetite and Obesity
- Peroxisome Proliferator-Activated Receptors
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Pharmacology and Obesity Treatment
- Gut microbiota and health
- Gastrointestinal motility and disorders
- Clinical Nutrition and Gastroenterology
- Muscle metabolism and nutrition
- Schizophrenia research and treatment
- Growth Hormone and Insulin-like Growth Factors
- Protein Interaction Studies and Fluorescence Analysis
- Health Policy Implementation Science
- Fatty Acid Research and Health
- Apelin-related biomedical research
Cedars-Sinai Medical Center
2012-2022
University of Southern California
1997-2011
LAC+USC Medical Center
2005
Karolinska Institutet
2001
Pennington Biomedical Research Center
1992
Northeast Ohio Medical University
1983
Ohio University
1983
BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women diverse ethnicities (27.5 ± 1.1 years age, BMI 25.4 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet,...
This study examined the relationship between transcapillary insulin transport and action in vivo. During euglycemic clamps (n = 7) normal conscious dogs we simultaneously measured plasma thoracic duct lymph glucose utilization (Rd). Clamps consisted of an activation phase with constant infusion (0.6 mU/kg per min) a deactivation phase. [14C]Inulin was infused as passively transported control substance. While [14C]inulin reached equilibrium lymph, steady-state (ss) higher than (P less 0.05)...
The relative roles of insulin sensitivity, secretion, and glucose effectiveness to the diurnal rhythm tolerance were examined in normal-weight (n = 12) obese 11) subjects. Two frequently sampled intravenous tests performed each subject at 0800 on one occasion 1800 a separate day. Tests preceded by identical fasts 10–12 h. In nonobese subjects, tolerance, expressed as 10- 16-min KG value (KGS), was much reduced evening (AM 2.98 ± 0.45, PM 1.86 0.33 min−1 P < 0.002). lower morning than...
Glucose disappearance after an oral or intravenous challenge is a function of the effects both endogenously secreted insulin and glucose itself. We previously introduced term “glucose effectiveness,” SG, defined as ability per se to enhance its own independent increment in plasma insulin. The present investigation, performed conscious dogs, was undertaken quantify this effect by minimal-model-based analysis dynamics frequently sampled tolerance test (FSIGT). values from standard FSIGT were...
Atypical antipsychotics have been linked to weight gain, hyperglycemia, and diabetes. We examined the effects of atypical olanzapine (OLZ) risperidone (RIS) versus placebo on adiposity, insulin sensitivity (SI), pancreatic β-cell compensation. Dogs were fed ad libitum given OLZ (15 mg/day; n = 10), RIS (5 or gelatin capsules (n 6) for 4–6 weeks. resulted in substantial increases adiposity: increased total body fat (+91 ± 20%; P 0.000001) reflecting marked subcutaneous (+106 24%; 0.0001)...
Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) systemically half the rate (0.025, 0.10, 0.50, 0.70, 1.5...
In vitro, insulin transport across endothelial cells has been reported to be saturable, suggesting that the process is receptor mediated. present study, of capillary was investigated in vivo. Euglycemic glucose clamps were performed anesthetized dogs (n = 16) which infused achieve concentrations physiological range (1.0 mU/kg per min + 5 priming bolus; n 8) or pharmacologic (18 325 8). Insulin measured plasma and hindlimb lymph derived from interstitial fluid (ISF) surrounding muscle. Basal...
There is wide variance among individuals in the fraction of insulin cleared by liver (20% to 80%). Hepatic clearance 67% lower African Americans than European Americans. Clearance also American children 7-13 years age. Lower hepatic will result peripheral hyperinsulinemia: this exacerbates resistance, which stresses β-cells, possibly resulting their ultimate failure and onset type 2 diabetes. We hypothesize that can be a primary cause diabetes at-risk individuals.
Insulin resistance is a powerful risk factor for Type 2 diabetes and constellation of chronic diseases, most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors insulin sensitivity under baseline, nonstimulated conditions.Metabolic assessment was performed in healthy dogs (n = 90). Whole-body from euglycemic clamps (SICLAMP ) the primary outcome variable, measured independently by IVGTT 36). Adiposity MRI 90), glucose-stimulated...
We set out to examine whether angiotensin-driven hypertension can alter insulin action and these changes are reflected as in interstitial (the signal which insulin-sensitive cells respond increase glucose uptake). To this end, we measured hemodynamic parameters, turnover, dynamics both plasma fluid (lymph) during hyperinsulinemic euglycemic clamps anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed mean arterial pressure, heart...
Glucose tolerance is determined by both insulin action and insulin-independent effects, or "glucose effectiveness," which includes glucose-mediated stimulation of glucose uptake (Rd) suppression hepatic output (HGO). Despite its importance to tolerance, controversy surrounds accurate assessment effectiveness. Furthermore, the relative contributions glucose's actions on Rd HGO under steady state dynamic conditions are unclear. We performed hyperglycemic clamps intravenous tests in eight...
Insulin action in vivo is determined by both transendothelial insulin transport (TET) across the capillary and subsequent binding postreceptor events. To examine TET under non-steady-state conditions, we performed intravenous glucose tolerance tests (IVGTT; 0.3 g/kg; n = 7) on conscious dogs. At basal, lymph was only 53 +/- 7% of plasma (P < 0.001), whereas exceeded levels (109 4 vs. 104 mg/dl, respectively; P 0.02). On injection, dynamics were similar, suggesting rapid equilibration...
NN304 [LysB29-tetradecanoyl des(B30) human insulin] is a potentially therapeutic insulin analog designed to exhibit protracted glucose-lowering action. In dogs with infusion rates similar itself, exhibits glucose uptake (Rd) stimulation delayed onset of This compartmental modeling study was determine if action could be accounted for by the ∼2% unbound concentration. (or insulin) (n = 6 each) infused at 10.2 pmol · min−1 kg−1 under euglycemic clamp conditions in anesthetized dogs. appearance...
We previously reported a striking similarity between the dynamics of both glucose turnover and thoracic duct lymph insulin during euglycemic clamps (J Clin Invest 84:1620, 1989), which suggested that transendothelial transport (TET) is rate-limiting for action in vivo. Thoracic lymph, however, primarily derived from insulin-insensitive tissues, raises questions as to physiological significance this relationship. The relationship TET was thus examined insulin-sensitive tissues by simultaneous...