ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2018
Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 39 citations in OpenAlex.
- Beneficial vascular effects of oral phosphatidylserine supplementation in type 2 diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Trial
- Six decades of animal accelerometry: trends, applications, and future directions.Movement ecology · 2026Review
- Metabolic Syndrome Predisposes Ossabaw Minipig Retina to an Early Neurodegenerative Milieu.Cells · 2026Article
- Sex-dependent effects of a high-fat diet-induced obesity model on cerebrovascular health and brain metabolism.Experimental physiology · 2025Article
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- Effect of insulin on indices of cerebral blood flow and cerebrovascular compliance in young adults.American journal of physiology. Heart and circulatory physiology · 2025Article
- Increased Stress Hyperglycemia Ratio Predicts Poor Clinical Outcome in Critically Ill COPD Patients: A Retrospective Study.International journal of chronic obstructive pulmonary disease · 2025Article
- Impact of sex and diet-induced weight loss on vascular insulin sensitivity in type 2 diabetes.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Western diet-induced obesity results in brain mitochondrial dysfunction in female Ossabaw swine.Frontiers in molecular neuroscience · 2023Article
- Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes.Frontiers in cardiovascular medicine · 2023Article
- New insights into mechanisms of endothelial insulin resistance in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2022Review
- The role of nitric oxide in flow-induced and myogenic responses in 1A, 2A, and 3A branches of the porcine middle cerebral artery.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine.Basic research in cardiology · 2022Article
- Loss of skeletal muscle mass is not specific to type 2 diabetes.World journal of diabetes · 2022Article
- Endothelial HSP72 is not reduced in type 2 diabetes nor is it a key determinant of endothelial insulin sensitivity.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- Article
- Molecular biochemical aspects of salt (sodium chloride) in inflammation and immune response with reference to hypertension and type 2 diabetes mellitus.Lipids in health and disease · 2021Review
- Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure.JCI insight · 2021Article
- The right ventricular transcriptome signature in Ossabaw swine with cardiometabolic heart failure: implications for the coronary vasculature.Physiological genomics · 2021Article
- Collagen matrix perturbations in corneal stroma of Ossabaw mini pigs with type 2 diabetes.Molecular vision · 2021Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
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Abstract
Impaired microvascular insulin signaling may develop before overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex), and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase Cβ (PKCβ). Juvenile Ossabaw miniature swine (3.5 mo of age) were divided into two groups: lean control ( n = 6) and obese ( n = 6). Obesity was induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 10 wk. Juvenile obesity was characterized by excess body mass, hyperglycemia, physical inactivity (accelerometer), and marked lipid accumulation in the skeletal muscle, with no evidence of overt atherosclerotic lesions in athero-prone regions, such as the abdominal aorta. Endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) vasomotor responses in the brachial and carotid arteries (wire myography), as well as in the skeletal muscle resistance and 2A pial arterioles (pressure myography) were unaltered, but insulin-induced microvascular vasodilation was impaired in the obese group. Blunted insulin-stimulated vasodilation, which was reversed with acute PKCβ inhibition (LY333-531), occurred alongside decreased tissue perfusion, as well as reduced insulin-stimulated Akt signaling in the prefrontal cortex, but not the triceps. In the early stages of juvenile obesity development, the microvasculature and prefrontal cortex exhibit impaired insulin signaling. Such adaptations may underscore vascular and neurological derangements associated with juvenile obesity.
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