The Expression of TNFα by Human Muscle: Relationship to Insulin Resistance

TNFα is overexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF (r = -0.60, P \u3c 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance

Ten Years In: Implementing Strategic Approaches to Cyberspace

This book represents a look beyond theories and analogies to examine the challenges of strategy implementation. In the essays that follow, practitioners who are building cyberspace forces at-scale join scholars who study power and force in this new domain to collectively offer a unique perspective on the evolution and future of cyber strategy and operations.https://digital-commons.usnwc.edu/usnwc-newport-papers/1044/thumbnail.jp

Canagliflozin extends life span in genetically heterogeneous male but not female mice.

Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases

Intramyocellular Lipid and Insulin Resistance: Differential Relationships in European and African Americans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93716/1/oby.2011.45.pd

Serum Apolipoproteins and Apolipopprotein-Defined Lipoprotein Subclasses: A Hypothesis-Generation Prospective Study of Cardiovascular Events in Type 1 Diabetes

Apolipoproteins and apolipoprotein-defined lipoprotein subclasses have been associated with dyslipidemia and cardiovascular disease (CVD). Our main objective was to define associations of serum apolipoproteins and ADLS with any CVD and major atherosclerotic cardiovascular events (MACE) in a prospective study of T1D. Serum apolipoproteins and ADLS (14 biomarkers in total) were measured in sera (obtained 1997-2000) from a subset (n=465) of the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort. Prospective associations of any CVD (myocardial infarction, stroke, confirmed angina, silent MI, revascularization, or congestive heart failure) and MACE (fatal or nonfatal myocardial infarction or stroke), over 5942 and 6180 patient-years follow-up respectively, were investigated using Cox proportional hazards models, unadjusted and adjusted for risk factors. During 15 years follow-up, 50 any CVD and 24 MACE events occurred. Nominally significant positive univariate associations with any CVD were APOB, APOC3 and its sub-fractions [heparin precipitate (HP), heparin soluble (HS)], and ADLS-defined Lp-B. Nominally significant positive univariate associations with MACE were APOC3 and sub-fractions, and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjustment for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLS with either any CVD or MACE. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACE in T1D adults

Making Connections: A Handbook for Effective Formal Mentoring Programs in Academia

This book, Making Connections: A Handbook for Effective Formal Mentoring Programs in Academia, makes a unique and needed contribution to the mentoring field as it focuses solely on mentoring in academia. This handbook is a collaborative institutional effort between Utah State University’s (USU) Empowering Teaching Open Access Book Series and the Mentoring Institute at the University of New Mexico (UNM). This book is available through (a) an e-book through Pressbooks, (b) a downloadable PDF version on USU’s Open Access Book Series website), and (c) a print version available for purchase on the USU Empower Teaching Open Access page, and on Amazon