Am J Physiol Endocrinol Metab
March 2024
Sodium glucose cotransporter 2 inhibitors (SGLT2is) improved major adverse cardiovascular events (MACE), heart failure, and renal outcomes in large trials; however, a thorough understanding of the vascular physiological changes contributing to these responses is lacking. We hypothesized that SGLT2i therapy would diminish vascular insulin resistance and improve hemodynamic function, which could improve clinical outcomes. To test this, we treated 11 persons with type 2 diabetes for 12 wk with 10 mg/day empagliflozin and measured vascular stiffness, endothelial function, peripheral and central arterial pressures, skeletal and cardiac muscle perfusion, and vascular biomarkers before and at 120 min of a euglycemic hyperinsulinemic clamp at and .
View Article and Find Full Text PDFContext: Vascular insulin resistance is commonly observed in obesity and diabetes; yet, insulin action across the vascular tree and the relationship between insulin responses at different vascular locations remains incompletely defined.
Objective: To elucidate the impact of elevated free fatty acids (FFAs) on insulin action across the arterial tree and define the relationship among insulin actions in the different arterial segments.
Methods: This randomized crossover study assigned healthy lean adults to 2 separate admissions with euglycemic insulin clamp superimposed for the final 120 minutes of 5-hour lipid or matched-volume saline infusion.
Insulin's microvascular actions and their relationship to insulin's metabolic actions have not been well studied in adults with type 1 diabetes mellitus (T1DM). We compared the metabolic and selected micro- and macrovascular responses to insulin by healthy adult control ( = 16) and subjects with T1DM ( = 15) without clinical microvascular disease. We measured insulin's effect on ) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), ) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and ) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp.
View Article and Find Full Text PDFBMJ Open Diabetes Res Care
January 2022
Introduction: Individuals with type 1 diabetes have increased arterial stiffness compared with age-matched healthy controls. Our aim was to determine which hemodynamic and demographic factors predict arterial stiffness in this population.
Research Design And Methods: Carotid-femoral pulse wave velocity (cfPWV) was examined in 41 young adults and adolescents with type 1 diabetes without microvascular complications.
Am J Physiol Endocrinol Metab
February 2022
Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance have not been defined.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
February 2022
Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1.
View Article and Find Full Text PDFInsulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications.
View Article and Find Full Text PDFIntroduction: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear.
Materials And Methods: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults.
Key Points: Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may themselves alter vascular function. No prior studies have examined the effect of acute hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations.
View Article and Find Full Text PDFDiabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared to normoglycemic controls. Currently there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiologic factors (e.
View Article and Find Full Text PDFObjective: Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.
View Article and Find Full Text PDFContext: Glucagon-like peptide-1 (GLP-1) and insulin increase muscle microvascular perfusion, thereby increasing tissue endothelial surface area and nutrient delivery.
Objective: To examine whether GLP-1 and insulin act additively on skeletal and cardiac microvasculature and conduit artery.
Design: Healthy adults underwent three study protocols in random order.
Context: Insulin reportedly impairs endothelial function in conduit arteries but improves it in resistance and microvascular arterioles in healthy humans. No studies have assessed endothelial function at three arterial levels in healthy or metabolic syndrome (METSYN) subjects.
Objective: The objective of the study was to compare endothelial responsiveness of conduit arteries, resistance, and microvascular arterioles to insulin in healthy and METSYN subjects.
Muscle microvascular surface area determines substrate and hormonal exchanges between plasma and muscle interstitium. GLP-1 (glucagon-like peptide-1) regulates glucose-dependent insulin secretion and has numerous extrapancreatic effects, including a salutary vascular action. To examine whether GLP-1 recruits skeletal and cardiac muscle microvasculature in healthy humans, 26 overnight-fasted healthy adults received a systemic infusion of GLP-1 (1.
View Article and Find Full Text PDFObjective: To test whether early, insulin-mediated microvascular recruitment in skeletal muscle predicts steady-state glucose metabolism in the setting of physiological elevation of free fatty acid concentrations.
Research Design And Methods: We measured insulin's microvascular and metabolic effects in 14 healthy young adults during a 2-h euglycemic insulin clamp. Plasma free fatty acid concentrations were raised (Intralipid and heparin infusion) for 3 h before the clamp and maintained at postprandial concentrations during the clamp.
J Clin Endocrinol Metab
July 2012
Context: Angiotensin II type 1 receptor (AT(1)R) tone restricts muscle microvascular blood volume (MBV) and decreases muscle insulin delivery and glucose use.
Objective: The objective of the study was to examine whether acute AT(1)R blockade alters microvascular perfusion in skeletal and cardiac muscle in humans.
Setting: The study was conducted at the General Clinical Research Center at the University of Virginia.
Objective: Insulin recruits muscle microvasculature, thereby increasing endothelial exchange surface area. Free fatty acids (FFAs) cause insulin resistance by activating inhibitor of κB kinase β. Elevating plasma FFAs impairs insulin's microvascular and metabolic actions in vivo.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
February 2011
Context: Insulin recruits microvasculature in both cardiac and skeletal muscle, which increases the endothelial exchange surface area. Plasma concentrations of free fatty acids (FFAs) are elevated in patients with diabetes, which impairs insulin-mediated skeletal muscle microvascular recruitment.
Objective: The objective of the study was to examine whether elevated FFAs likewise cause insulin resistance in cardiac muscle microvasculature.
J Clin Endocrinol Metab
September 2009
Context: Insulin recruits muscle microvasculature, which increases the endothelial exchange surface area to facilitate substrate delivery. Elevated plasma concentrations of free fatty acids (FFAs) cause insulin resistance.
Objectives: The aim of the study was to examine whether FFAs cause insulin resistance in human muscle microvasculature.
Objective: Ingestion of a mixed meal recruits flow to muscle capillaries and increases total forearm blood flow in healthy young lean people. We examined whether these vascular responses are blunted by obesity.
Research Design And Methods: We fed eight middle-aged lean and eight obese overnight-fasted volunteers a liquid mixed meal (480 kcal).
Context: Endothelial dysfunction is common in patients with GH deficiency who are at increased risk for premature cardiovascular death. GH regulates vascular tone and reactivity in humans.
Objective: Our objective was to explore the mechanisms underlying the GH's acute vascular effects.
Objective: Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
June 2006
Intense exercise and insulin each increases total limb blood flow and recruits muscle capillaries, presumably to facilitate nutrient exchange. Whether mixed meals or light exercise likewise recruits capillaries is unknown. We fed 18 (9 M, 9 F) healthy volunteers a 480-kcal liquid mixed meal.
View Article and Find Full Text PDFWe have previously shown that skeletal muscle capillaries are rapidly recruited by physiological doses of insulin in both humans and animals. This facilitates glucose and insulin delivery to muscle, thus augmenting glucose uptake. In obese rats, both insulin-mediated microvascular recruitment and glucose uptake are diminished; however, this action of insulin has not been studied in obese humans.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
August 2004
Amino acids are unique anabolic agents in that they nutritively signal to mRNA translation initiation and serve as substrates for protein synthesis in skeletal muscle. Glucocorticoid excess antagonizes the anabolic action of amino acids on protein synthesis in laboratory animals. To examine whether excessive glucocorticoids modulate mixed amino acid-signaled translation initiation in human skeletal muscle, we infused an amino acid mixture (10% Travasol) systemically to 16 young healthy male volunteers for 6 h in the absence (n = 8) or presence (n = 8) of glucocorticoid excess (dexamethasone 2 mg orally every 6 h for 3 days).
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