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Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention ( þ 52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P ¼ 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses. NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow. [ABSTRACT FROM AUTHOR]

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n = 13), with at least one parent with T2D (FH+, n = 14) and clinically diagnosed T2D (n = 11) underwent a mixed meal challenge (MMC). Metabolic responses [blood glucose, plasma insulin, plasma nonesterified fatty acids (NEFAs), and fat oxidation] were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 min post-MMC. FHþ had normal blood glucoses, increased adiposity, and impaired post-MMC adipose tissue MBF (Δ0.70 ± 0.22 vs. 2.45 ± 0.60 acoustic intensity/s, P = 0.007) and post-MMC adipose tissue insulin resistance (Adipo-IR index; Δ45.5 ± 13.9 vs. 7.8 ± 5.1 mmol/L × pmol/L, P = 0.007) compared with FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (iAUC) (35-55 min post-MMC, iAUC) was higher in FH+ and T2D than in FH- (P = 0.005 and 0.009, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (P = 0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D. [ABSTRACT FROM AUTHOR]

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (25%, 27%, and 46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (37%, 46%, and 64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction (R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial. [ABSTRACT FROM AUTHOR]

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase- μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ+/+ and nNOSμ-/- mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ+/+ and nNOSμ-/-, respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ-/- mice, and exercise increased NOS activity only in nNOSμ+/+ mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg-1·min-1, P · 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ-/- than in nNOSμ+/+ mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ-/- mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ-/- mice may be due to compensatory increases in AMPK activation. [ABSTRACT FROM AUTHOR]