Induction of Type 2 Diabetes in Mice to Understand Vascular Changes That Drive Diabetic Retinopathy.

Diabetic retinopathy is a common complication of type 2 diabetes. Research into this comorbidity is challenging due to the slow progression of pathological changes and the limited transgenic models available to study disease progression and mechanistic changes. Here, we describe a non-transgenic mouse model of accelerated type 2 diabetes using a high-fat diet in combination with streptozotocin delivered via osmotic mini pump. This model, when subjected to fluorescent gelatin vascular casting, can be used to study vascular changes in type 2 diabetic retinopathy.

Recovery of chloroplast genomes from medieval millet grains excavated from the Areni-1 cave in southern Armenia.

Panicum miliaceum L. was domesticated in northern China at least 7000 years ago and was subsequentially adopted in many areas throughout Eurasia. One such locale is Areni-1 an archaeological cave site in Southern Armenia, where vast quantities archaeobotanical material were well preserved via desiccation. The rich botanical material found at Areni-1 includes P. miliaceum grains that were identified morphologically and14C dated to the medieval period (873 ± 36 CE and 1118 ± 35 CE). To investigate the demographic and evolutionary history of the Areni-1 millet, we used ancient DNA extraction, hybridization capture enrichment, and high throughput sequencing to assemble three chloroplast genomes from the medieval grains and then compared these sequences to 50 modern P. miliaceum chloroplast genomes. Overall, the chloroplast genomes contained a low amount of diversity with domesticated accessions separated by a maximum of 5 SNPs and little inference on demography could be made. However, in phylogenies the chloroplast genomes separated into two clades, similar to what has been reported for nuclear DNA from P. miliaceum. The chloroplast genomes of two wild (undomesticated) accessions of P. miliaceum contained a relatively large number of variants, 11 SNPs, not found in the domesticated accessions. These results demonstrate that P. miliaceum grains from archaeological sites can preserve DNA for at least 1000 years and serve as a genetic resource to study the domestication of this cereal crop.

Discovering the Secrets of Ancient Plants: Recovery of DNA from Museum and Archaeological Plant Specimens.

Plant DNA preserved in ancient specimens has recently gained importance as a tool in comparative genomics, allowing the investigation of evolutionary processes in plant genomes through time. However, recovering the genomic information contained in such specimens is challenging owing to the presence of secondary substances that limit DNA retrieval. In this chapter, we provide a DNA extraction protocol optimized for the recovery of DNA from degraded plant materials. The protocol is based on a commercially available DNA extraction kit that does not require handling of hazardous reagents.

Impaired postprandial adipose tissue microvascular blood flow responses to a mixed-nutrient meal in first-degree relatives of adults with type 2 diabetes.

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. FH+ 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.NEW & NOTEWORTHY Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.

Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes.

AIMS/HYPOTHESIS: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. METHODS: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. RESULTS: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p < 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p < 0.01) and FH+ (1.3-fold, p < 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p < 0.01), brachial artery diameter (1.1-fold, p < 0.01) and brachial artery blood flow (1.7-fold, p < 0.001) and reduced vascular resistance (0.7-fold, p < 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p < 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. CONCLUSIONS/INTERPRETATION: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC.

An Abductive Inference Approach to Assess the Performance-Enhancing Effects of Drugs Included on the World Anti-Doping Agency Prohibited List.

Some have questioned the evidence for performance-enhancing effects of several substances included on the World Anti-Doping Agency's Prohibited List due to the divergent or inconclusive findings in randomized controlled trials (RCTs). However, inductive statistical inference based on RCTs-only may result in biased conclusions because of the scarcity of studies, inter-study heterogeneity, too few outcome events, or insufficient power. An abductive inference approach, where the body of evidence is evaluated beyond considerations of statistical significance, may serve as a tool to assess the plausibility of performance-enhancing effects of substances by also considering observations and facts not solely obtained from RCTs. Herein, we explored the applicability of an abductive inference approach as a tool to assess the performance-enhancing effects of substances included on the Prohibited List. We applied an abductive inference approach to make inferences on debated issues pertaining to the ergogenic effects of recombinant human erythropoietin (rHuEPO), beta2-agonists and anabolic androgenic steroids (AAS), and extended the approach to more controversial drug classes where RCTs are limited. We report that an abductive inference approach is a useful tool to assess the ergogenic effect of substances included on the Prohibited List-particularly for substances where inductive inference is inconclusive. Specifically, a systematic abductive inference approach can aid researchers in assessing the effects of doping substances, either by leading to suggestions of causal relationships or identifying the need for additional research.

Femoral Heads from Total Hip Arthroplasty as a Source of Adult Hematopoietic Cells.

Normal human bone marrow cells are critical for studies of hematopoiesis and as controls to assess toxicity. As cells from commercial vendors are expensive, many laboratories resort to cancer-free bone marrow specimens obtained during staging or to umbilical cord blood cells, which may be abnormal or reflect a much younger age group compared to the disease samples under study. We piloted the use of femoral heads as an alternative and inexpensive source of normal bone marrow. Femoral heads were obtained from 21 successive patients undergoing elective hip arthroplasty. Mononuclear cells (MNCs) were purified with Ficoll, and CD3+, CD14+, and CD34+ cells were purified with antibody-coated microbeads. The median yield of MNCs was 8.95 × 107 (range, 1.62 × 105-2.52 × 108), and the median yield of CD34+ cells was 1.40 × 106 (range, 3.60 × 105-9.90 × 106). Results of downstream applications including qRT-PCR, colony-forming assays, and ex vivo proliferation analysis were of high quality and comparable to those obtained with standard bone marrow aspirates. We conclude that femoral heads currently discarded as medical waste are a cost-efficient source of bone marrow cells for research use.

In utero exposure to diesel exhaust particles, but not silica, alters post-natal immune development and function.

Our understanding of the impact of in utero exposure to PM on post-natal immune function and the subsequent response to PM exposure is limited. Similarly, very few studies have considered the effect of exposure to PM from different sources. Thus, the aim of this study was to examine how in utero exposure to PM from different sources effects the post-natal response to pro-inflammatory and immune stimuli. C56BL/6J pregnant mice were exposed intranasally on gestational day (E)7.5, E12.5 and E17.5-50 µg of diesel exhaust particles (DEP), silica or saline. At 4-weeks post-natal age, sub-groups of male and female mice were exposed intranasally to 50 µg of DEP or saline. Lung inflammatory responses were assessed 6 h later by quantifying inflammatory cells and cytokine production (MCP-1, MIP-2, IL-6). In separate groups of mice, the spleen was harvested to quantify B and T cell populations. Splenocytes were isolated and exposed to lipopolysaccharide or poly I:C for assessment of cytokine production. Exposure to DEP in utero decreased %CD1dhighCD5+ B cells in female mice and IFN-γ production by splenocytes in both sexes. Male mice had elevations in macrophage and lymphocyte numbers in response to DEP whereas female mice only had elevated IL-6, MCP-1 and MIP-2 levels. In utero exposure to silica had no effect on these measures. These data suggest that in utero exposure to PM alters immune development and post-natal immune function. This response is dependent on the source of PM, which has implications for understanding the community health effects of exposure to air pollution.

Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic-euglycaemic clamp.

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic-euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin-stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin-resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially-with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides-compared to the hyperinsulinaemic-euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.

Metformin improves vascular and metabolic insulin action in insulin-resistant muscle.

Insulin stimulates glucose disposal in skeletal muscle in part by increasing microvascular blood flow, and this effect is blunted during insulin resistance. We aimed to determine whether metformin treatment improves insulin-mediated glucose disposal and vascular insulin responsiveness in skeletal muscle of insulin-resistant rats. Sprague-Dawley rats were fed a normal (ND) or high-fat (HFD) diet for 4 weeks. A separate HFD group was given metformin in drinking water (HFD + MF, 150 mg/kg/day) during the final 2 weeks. After the intervention, overnight-fasted (food and metformin removed) anaesthetised rats underwent a 2-h euglycaemic-hyperinsulinaemic clamp (10 mU/min/kg) or saline infusion. Femoral artery blood flow, hindleg muscle microvascular blood flow, muscle glucose disposal and muscle signalling (Ser473-AKT and Thr172-AMPK phosphorylation) were measured. HFD rats had elevated body weight, epididymal fat pad weight, fasting plasma insulin and free fatty acid levels when compared to ND. HFD-fed animals displayed whole-body and skeletal muscle insulin resistance and blunting of insulin-stimulated femoral artery blood flow, muscle microvascular blood flow and skeletal muscle insulin-stimulated Ser473-AKT phosphorylation. Metformin treatment of HFD rats reduced fasting insulin and free fatty acid concentrations and lowered body weight and adiposity. During euglycaemic-hyperinsulinaemic clamp, metformin-treated animals showed improved vascular responsiveness to insulin, improved insulin-stimulated muscle Ser473-AKT phosphorylation but only partially restored (60%) muscle glucose uptake. This occurred without any detectable levels of metformin in plasma or change in muscle Thr172-AMPK phosphorylation. We conclude that 2-week metformin treatment is effective at improving vascular and metabolic insulin responsiveness in muscle of HFD-induced insulin-resistant rats.

Advantages of an Anterior-Based Muscle-Sparing Approach in Transitioning From a Posterior Approach for Total Hip Arthroplasty: Minimizing the Learning Curve.

BACKGROUND: Enthusiasm for anterior-based approaches for total hip arthroplasty (THA) continues to increase but there is concern for increased complications during the learning curve period associated. This study aimed to investigate if there was a difference in perioperative variables, intraoperative and immediate postoperative complications, or patient-reported outcomes when transitioning from a mini-posterior approach (mPA) to an anterior-based muscle-sparing (ABMS) approach for THA. METHODS: Retrospective cohort study on the first 100 primary THA cases (n = 96 patients) of the senior author (August 2016 to August 2017) using the ABMS approach. These cases were compared to primary THA cases done the year prior (July 2015 to July 2016, n = 91 cases in 89 patients) using an mPA. Data were extracted and analyzed via gamma regression with robust standard errors and using generalized estimating equation regression. RESULTS: We found no difference in the estimated blood loss (P = .452) and surgical time (P = .564) between the cohorts. The ABMS cases had a slightly shorter length of stay (P = .001) with an adjusted mean length of stay of 1.53 days (95% confidence interval 1.4-1.6) compared to 1.85 days (95% confidence interval 1.8-1.9) in the mPA cases. There was no difference in the frequency of immediate postoperative complications (all, P > .05). There was no difference in the adjusted mean change in patient-reported outcomes (all P > .05). In the ABMS group, there was no difference in surgical time or physical function computerized adaptive test between the first 20 cases (reference) and each subsequent group of 20 cases (all P > .05). CONCLUSION: This study demonstrates no associated learning curve for an experienced senior surgeon when switching routine THA approach from mPA to ABMS. We advise careful interpretation of our results, as they may not apply to all surgeons and practices. LEVEL OF EVIDENCE: Level III Therapeutic Study: retrospective comparative study.

Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome.

Purpose: Sjögren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6lpr [MRL/lpr]) of Sjögren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain- and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. Methods: Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. Results: Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. Conclusions: Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.

Pregnancy protects against the pro-inflammatory respiratory responses induced by particulate matter exposure.

BACKGROUND: Little is known about the effect of pregnancy on the response to particulate matter. The aim of this study was to determine if pregnancy increases the susceptibility to PM from different sources using a mouse model. METHODS: Pregnant, eight-week-old C57BL/6J mice were exposed intranasally to 50 µg of diesel exhaust particles (DEP), iron oxide (Fe2O3) or silica (SiO2) in 50 µL of saline, or saline alone, on gestational day (E)7.5, E12.5 and E17.5. Groups of non-pregnant mice were exposed on day (D)0, D5 and D10. Biological samples were collected 24 h after the last exposure. Serum IL-4 and IL-6 levels were quantified by ELISA. Bronchoalveolar lavage (BAL) fluid was collected for inflammatory cells counts and assessment of IFN-É£, IL-4, IL-5, IL-6, IL-8 and IL-10 levels by ELISA. The spleen and thymus were also collected and the percentage of B cells and CD4+, CD8+ and CD4+CD25 + T cells were determined by flow cytometry. RESULTS: Exposure to silica caused an influx of lymphocytes, eosinophils and neutrophils into the lung. The magnitude of this response was suppressed by pregnancy. Pregnancy also enhanced the production of CD4+CD25 + T cells in response to DEP and silica exposure. CONCLUSIONS: Collectively, our data suggest that pregnancy reduces the inflammatory response to silica and alters the immune response to DEP. These responses were accompanied by pregnancy related changes including increased IL-4 production, reduced IL-8 production and an increase in the proportion of CD4+CD25 + T cells in response to PM exposure.

Low-cost cross-taxon enrichment of mitochondrial DNA using in-house synthesised RNA probes.

Hybridization capture with in-solution oligonucleotide probes has quickly become the preferred method for enriching specific DNA loci from degraded or ancient samples prior to high-throughput sequencing (HTS). Several companies synthesize sets of probes for in-solution hybridization capture, but these commercial reagents are usually expensive. Methods for economical in-house probe synthesis have been described, but they do not directly address one of the major advantages of commercially synthesised probes: that probe sequences matching many species can be synthesised in parallel and pooled. The ability to make "phylogenetically diverse" probes increases the cost-effectiveness of commercial probe sets, as they can be used across multiple projects (or for projects involving multiple species). However, it is labour-intensive to replicate this with in-house methods, as template molecules must first be generated for each species of interest. While it has been observed that probes can be used to enrich for phylogenetically distant targets, the ability of this effect to compensate for the lack of phylogenetically diverse probes in in-house synthesised probe sets has not been tested. In this study, we present a refined protocol for in-house RNA probe synthesis and evaluated the ability of probes generated using this method from a single species to successfully enrich for the target locus in phylogenetically distant species. We demonstrated that probes synthesized using long-range PCR products from a placental mammal mitochondrion (Bison spp.) could be used to enrich for mitochondrial DNA in birds and marsupials (but not plants). Importantly, our results were obtained for approximately a third of the cost of similar commercially available reagents.

Correction: Low-cost cross-taxon enrichment of mitochondrial DNA using in-house synthesised RNA probes.

[This corrects the article DOI: 10.1371/journal.pone.0209499.].

Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle.

AIMS: Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin's microvascular and metabolic actions in skeletal muscle. METHODS AND RESULTS: Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals' systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin's effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake. CONCLUSIONS: Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin's microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome.

Purpose: Sjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands. Methods: Lacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software. Results: Our results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes. Conclusions: These data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = -0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.