A5010910025- Diabetes Management and Research
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Diabetes and associated disorders
- Diabetes Treatment and Management
- Heart Rate Variability and Autonomic Control
- Regulation of Appetite and Obesity
- Diabetes Management and Education
- Diet and metabolism studies
- Cardiovascular Function and Risk Factors
- Muscle metabolism and nutrition
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Liver Disease Diagnosis and Treatment
- Pharmacology and Obesity Treatment
- Neuroscience and Neuropharmacology Research
- Retinal Imaging and Analysis
- Pharmacological Effects and Assays
- Retinal Diseases and Treatments
- Neuroscience of respiration and sleep
- Sleep and Wakefulness Research
- Cardiac electrophysiology and arrhythmias
- Cardiovascular and exercise physiology
University of Kentucky
2022-2025
Lexington VA Health Care System
2024
Musgrove Park Hospital
2023
Ann Arbor Center for Independent Living
2020-2023
University of Utah
2016-2022
Diabetes Australia
2003-2019
Washington University in St. Louis
2008-2016
Joslin Diabetes Center
2003-2005
Harvard University
2003-2005
Harvard University Press
2003
Activation of peroxisome proliferator-activated receptor γ (PPARγ) by thiazolidinediones (TZDs) improves insulin resistance increasing insulin-stimulated glucose disposal in skeletal muscle. It remains debatable whether the effect TZDs on muscle is direct or indirect via adipose tissue. We therefore generated mice with muscle-specific PPARγ knockout (MuPPARγKO) using Cre/loxP recombination. Interestingly, MuPPARγKO developed excess adiposity despite reduced dietary intake. Although uptake...
Insulin receptors (IRs) on vascular endothelial cells have been suggested to participate in insulin-regulated glucose homeostasis. To directly address the role of insulin action function, we generated a cell IR knockout (VENIRKO) mouse using Cre-loxP system. Cultured endothelium VENIRKO mice exhibited complete rearrangement gene and more than 95% decrease mRNA. were born at expected Mendelian ratio, grew normally, fertile, normal patterns vasculature retina other tissues. Glucose homeostasis...
We and others have suggested that insulin predominantly acts indirectly to inhibit hepatic glucose production (HGP) via suppression of gluconeogenic precursors, FFAs, glucagon. To test hypothesis, we performed high-dose hyperinsulinemic-euglycemic clamps using [3-3H]-glucose in liver-specific receptor knockout (LIRKO) mice, LIRKO mice treated with streptozotocin (LIRKO+STZ), controls. In fasted was normal, but levels were elevated tenfold. STZ treatment reduced insulinemia by 60% resulting...
For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how fatal, hyperinsulinemic, hypoglycemic (10–15 mg/dL) clamps were performed in Sprague-Dawley rats simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested that: 1) antecedent glycemic control impacts mortality associated hypoglycemia; 2) limitation hypokalemia, potassium...
Insulin-induced severe hypoglycemia causes brain damage. The hypothesis to be tested was that diabetes portends more extensive tissue damage following an episode of hypoglycemia. Nine-week-old male streptozotocin-diabetic (DIAB; n = 10) or vehicle-injected control (CONT; 7) Sprague-Dawley rats were subjected hyperinsulinemic (0.2 U·kg −1 ·min ) hypoglycemic (10–15 mg/dl) clamps while awake and unrestrained. Groups precisely matched for depth duration (1 h) (CONT 11 ± 0.5 DIAB 12 0.2 mg/dl, P...
Low birth weight (LBW) is an important risk factor for type 2 diabetes. We have developed a mouse model of LBW resulting from undernutrition during pregnancy. Restriction maternal food intake day 12.5 to 18.5 pregnancy results in 23% decrease (P < 0.001), with normalization after birth. However, offspring pregnancies develop progressive, severe glucose intolerance by 6 months. To identify early defects that are responsible this phenotype, we analyzed mice at age months, before the onset...
OBJECTIVE Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports cognitive impairment due to hypoglycemia have been highly variable. It was hypothesized that recurrent preconditions brain protects against damage caused by hypoglycemia. RESEARCH DESIGN AND METHODS Nine-week-old male Sprague-Dawley rats were subjected either 3 consecutive days (25–40 mg/dl) (RH) or saline injections. On fourth day, a...
OBJECTIVE An impaired ability to sense and appropriately respond insulin-induced hypoglycemia is a common serious complication faced by insulin-treated diabetic patients. This study tests the hypothesis that insulin acts directly in brain regulate critical glucose-sensing neurons hypothalamus mediate counterregulatory response hypoglycemia. RESEARCH DESIGN AND METHODS To delineate actions brain, neuron-specific receptor knockout (NIRKO) mice littermate controls were subjected graded...
GLUT4 in muscle and adipose tissue is important maintaining glucose homeostasis. However, the role of insulin-responsive central nervous system has not been well characterized. To assess its importance, a selective knockout brain (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO had 99% reduction protein expression throughout brain. Despite normal feeding fasting glycemia, were intolerant, demonstrated hepatic insulin resistance, reduced uptake In response to...
OBJECTIVE This study aimed to 1) identify the frequency of severe and level 2 hypoglycemia presenting in individuals with type 1 diabetes using continuous glucose monitoring systems (CGMs), including those concomitant closed-loop insulin pumps, a clinical practice setting 2) evaluate impact beliefs around development this population. RESEARCH DESIGN AND METHODS A cross-sectional survey adults CGMs &gt;6 months was conducted at large tertiary academic center. Participant demographics,...
Hypoglycemia, hypoglycemia unawareness, and impaired counterregulation are major challenges to the intensive management of type 1 diabetes. While counterregulatory response is predominantly determined by degree duration hypoglycemia, there now evidence that insulin per se may influence hypoglycemia. To define role action in central nervous system regulating mice with a brain/neuron-specific receptor knockout (NIRKO) littermate controls were subjected 90-min hyperinsulinemic (20 mU · kg−1...
Class Ia phosphoinositide (PI) 3-kinases are heterodimers composed of a regulatory and catalytic subunit essential for the metabolic actions insulin. In addition to p85alpha p85beta, insulin-sensitive tissues such as fat, muscle, liver express splice variants pik3r1 gene, p50alpha p55alpha. To define role these variants, we have created mice with deletion p55alpha by using homologous recombination. These viable, grow normally, maintain normal blood glucose levels but lower fasting insulin...
Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up 60 min of recovery. To determine the importance endogenous insulin secretion during intense exercise, responses lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared those control (C; n = 6). Three iv protocols employed: hyperglycemic (HG; 7) euglycemic (EG1; 6)...
The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase action are effective therapies in type 2 diabetes mellitus (T2DM). However, is blunted T2DM, GIP-based have not been developed. Thus, it important to our understanding of the mechanisms action. We developed mice lacking GIP-producing K cells. Like humans with "GIP/DT" animals exhibited a normal secretory response exogenous but GIP. Pharmacologic doses xenin-25, another peptide produced by...
OBJECTIVE Evidence suggests that insulin-sensitive glucose transporters (GLUTs) other than GLUT4 may exist. To investigate whether GLUT12 represent another GLUT, transgenic (TG) mice overexpress were characterized. RESEARCH DESIGN AND METHODS TG overexpressed under a β-actin promoter generated. Glucose metabolism in and wild-type control was compared using insulin tolerance tests hyperinsulinemic-euglycemic clamps. In addition, basal insulin-stimulated clearance rates into peripheral tissues...