We have reported that insulin exerts two vascular actions in muscle; it both increases blood flow and recruits capillaries. In parallel hyperinsulinemic-euglycemic clamp studies, we compared the insulin dose response of muscle microvascular recruitment and femoral blood flow as well as hindleg glucose uptake in fed, hooded Wistar and fasted Sprague-Dawley rats. Using insulin doses between 0 and 30 mU ؊1 ⅐ min ؊1 ⅐ kg ؊1 , we measured microvascular recruitment at 2 h by 1-methylxanthine (1-MX) metabolism or contrast-enhanced ultrasound (CEU), and muscle glucose uptake was measured by either arteriovenous differences or using 2-deoxyglucose. We also examined the time course for reversal of microvascular recruitment following cessation of a 3 mU ⅐ min ؊1 ⅐ kg ؊1 insulin infusion. In both groups, whether measured by 1-MX metabolism or CEU, microvascular recruitment was fully activated by physiologic hyperinsulinemia and occurred at lower insulin concentrations than those that stimulated glucose uptake or hindleg total blood flow. The latter processes were insulin dose dependent throughout the entire dose range studied. Upon stopping the insulin infusion, increases in microvascular volume persisted for 15-30 min after insulin concentrations returned to basal levels. We conclude that the precapillary arterioles that regulate microvascular recruitment are more insulin sensitive than resistance arterioles that regulate total flow. Diabetes 53: [447][448][449][450][451][452][453] 2004 B ased in part on their observation that glucose disposal and leg blood flow displayed similar dose responses to insulin, Baron and colleagues (1,2) proposed that insulin-induced changes in blood flow were one determinant of muscle glucose uptake. Others (3,4) suggested that insulin-induced changes in flow require higher concentrations and longer exposures to insulin than those required for glucose disposal. We reported previously that insulin recruits microvascular vessels in skeletal muscle separate from any effect on total flow (5) and have suggested that insulin's microvascular action contributes to its overall effect on nutrient and hormone delivery to muscle (6). The effects of insulin on both capillary recruitment (7) and larger resistance vessels that regulate total blood flow to muscle (8) are the result of insulin-induced nitric oxide-dependent relaxation processes. We recently reported that microvascular recruitment by physiologic insulin precedes the increase in rat hindlimb total muscle blood flow by as much as 90 min (9). To further compare insulin's actions on total flow and microvascular recruitment, we examined the dose-response characteristics of these two vascular responses. In addition, to further characterize insulin's microvascular action, we examined the time course for its reversal following insulin removal. Dose-response studies were conducted on ad libitum-fed and 24-h-fasted rats using two different methods to assess microvascular recruitment, hindlimb metabolism of 1-methylxanthine (1-MX) (5) and contrast-enha...

Distinctive magmatic-hydrothermal tourmaline-rich features have developed in the Heemskirk and Pieman Heads granites from western Tasmania, Australia. They are categorized as tourmaline-rich patches, orbicules, cavities, and veins, based on their distinctive morphologies, sizes, mineral assemblages, and contact relationships with host granites. These textural features occur in discrete layers in the roof zone of granitic sills within the Heemskirk and Pieman Heads granites.Tourmaline patches commonly occur below a tourmaline orbicule-rich granitic sill. Tourmaline-filled cavities have typically developed above the tourmaline-quartz orbicules in the upper layer of the white phase of the Heemskirk Granite. Tourmaline-quartz veins penetrate all exposed levels of the granites, locally cutting tourmaline orbicules and cavities.The tourmalines are mostly schorl (Fe-rich) and foitite, with an average end-member component of schorl45 dravite6 tsilaisite1 uvite0 Fe-uvite3 foitite31 Mg-foitite4 olenite10. Element substitutions of the tourmalines are controlled by FeMg-1, Y Al X □(R 2+ Na)-1, and minor Y AlO(R 2+ OH)-1 (where R 2+ = Fe 2+ + Mg 2+ + Mn 2+ ) exchange vectors. A number of trace elements in tourmaline have consistent chemical evolutions grouped from tourmaline patches, through orbicules and cavities, to veins. There is a progressive decrease of most transition and large ion lithophile elements, and a gradual increase of most high field strength elements. These compositional variations in the different tourmaline-rich features probably relate to element partitioning occurring in these phases due to volatile exsolution and fluxing of aqueous boron-rich fluids that separated from the granitic melts during the emplacement of S-type magmas into the shallow crust (4 to 5.5 km).

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TNF-α is elevated in many states of insulin resistance, and acutely administered TNF-α in vivo inhibits insulin-mediated hemodynamic effects and glucose uptake in muscle. In this study, we assess whether the inhibitory effects of TNF-α are affected by insulin dose or muscle contraction. Whole body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg vascular resistance, hindleg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R′g) and hindleg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, were determined. Three groups were studied with and without infusion of TNF-α: euglycemic insulin-clamped, one-leg field-stimulated (2 Hz, 0.1 ms at 30 V), and saline-infused control anesthetized rats. Insulin infusions were 3, 10, or 30 mU · kg-1 · min-1 for 2 h. 1-MX metabolism was maximally increased by all three doses of insulin. GIR, HGU, and R′g were maximal at 10 mU and FBF was maximal at 30 mU of insulin. Contraction increased FBF, HGU, and 1-MX. TNF-α (0.5 μg · kg-1 · h-1) totally blocked the 3 and 10 mU insulin-mediated increases in FBF and 1-MX, and partly blocked GIR, HGU, and R′g. None of the increases due to twitch contraction was affected by TNF-α, and only the increase in FBF due to 30 mU of insulin was partly affected. We conclude that muscle capillary recruitment and glucose uptake due to high levels of insulin or muscle contraction under twitch stimuli at 2 Hz are resistant to TNF-α. These findings may have implications for ameliorating muscle insulin resistance resulting from increased plasma TNF-α and for the differing mechanisms by which contraction and insulin recruit capillary flow in muscle.

BackgroundLarge scale association studies have found a significant association between type 2 diabetes mellitus (T2DM) and transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146. However, the quality of data varies greatly, as the studies report inconsistent results in different populations. Hence, we perform this meta-analysis to give a more convincing result.MethodsThe articles, published from January 1st, 2000 to April 1st, 2017, were identified by searching in PubMed and Google Scholar. A total of 56628 participants (34232 cases and 22396 controls) were included in the meta-analysis. A total of 28 studies were divided into 4 subgroups: Caucasian (10 studies), East Asian (5 studies), South Asian (5 studies) and Others (8 studies). All the data analyses were analyzed by the R package meta.ResultsThe significant association was observed by using the dominant model (OR = 1.41, CI = 1.36 - 1.47, p < 0.0001), recessive model (OR = 1.58, CI = 1.48 - 1.69, p < 0.0001), additive model(CT vs CC) (OR = 1.34, CI = 1.28-1.39, p < 0.0001), additive model(TT vs CC) (OR = 1.81, CI = 1.69-1.94, p < 0.0001)and allele model (OR = 1.35, CI = 1.31-1.39, p < 0.0001).ConclusionThe meta-analysis suggested that rs7903146 was significantly associated with T2DM in Caucasian, East Asian, South Asian and other ethnicities.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0553-5) contains supplementary material, which is available to authorized users.