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Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer's disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was observed. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P

Growth hormone (GH) signaling is essential for heart development. Both GH deficiency and excess raise cardiovascular risk. Human (h) and mouse (m) GH differ structurally and functionally: hGH binds both the GH receptor (GHR) and prolactin receptor (PRLR), whereas mGH binds only GHR; thus, there is the potential for differential effects. We generated transgenic (hGH-TG) mice that produce pituitary hGH in response to hypothalamic signaling. These mice grow at the same rate as mGH-expressing wild-type (mGH-WT) mice but are smaller and have higher body fat. Echocardiography was used here to compare hGH-TG and mGH-WT mouse hearts. Male hGH-TG mice show a 48% lower left ventricular mass, 36% lower stroke volume, and 48% reduced cardiac output, resembling GH deficiency. Diastolic dysfunction, restrictive ventricular filling, and lower heart rate are suggested in hGH-TG mice. No significant differences in ejection fraction or fractional shortening were observed, even after high-fat diet (HFD) stress. HFD did not affect RNA markers of cardiac damage, although a possible association between B-type natriuretic peptide RNA levels and heart rate was detected. These observations suggest that diastolic dysfunction related to hGH and/or low GH might be offset by a lower heart rate, while structural changes precede functional effects. [ABSTRACT FROM AUTHOR]

Introduction Type 2 diabetes (T2D) is a complex metabolic syndrome, partly characterized by disordered glucose transport and disrupted insulin signaling (Javeed and Matveyenko 2018). A poor diet is one of [...], Sarco(endo)plasmic reticulum calcium ([Ca.sup.2+]) ATPase (SERCA) transports [Ca.sup.2+] in muscle. Impaired SERCA activity may contribute to diabetic myopathy. Sirtuin (SIRT) 3 regulates muscle metabolism and function; however, it is unknown if SIRT3 regulates muscle SERCA activity or acetylation. We determined if SIRT3 overexpression enhances SERCA activity in mouse gastrocnemius muscle and if SIRT3 overexpression preserves gastrocnemius SERCA activity in a model of type 2 diabetes, induced by high fat - high sucrose (HFHS) feeding. We also determined if the acetylation status of SERCA proteins in mouse gastrocnemius is altered by SIRT3 overexpression or HFHS feeding. Wild-type (WT) and SIRT3 transgenic ([SIRT3.sub.TG]) mice, overexpressing SIRT3 in skeletal muscle, were fed a standard or HFHS diet for 4 months. [SIRT3.sub.TG] and WT mice developed obesity and glucose intolerance after 4 months of HFHS feeding. SERCA [V.sub.max] was higher in gastrocnemius of [SIRT3.sub.TG] mice compared with WT mice. HFHS-fed mice had lower SERCA1a protein levels and lower SERCA [V.sub.max] in their gastrocnemius than control-fed mice. The decrease in SERCA [V.sub.max] in gastrocnemius muscle due to HFHS feeding was attenuated by SIRT3 overexpression in HFHS-fed [SIRT3.sub.TG] mice. SERCA1a and SERCA2a acetylation in mouse gastrocnemius was not altered by genotype or diet. These findings suggest SIRT3 overexpression improves SERCA function in mouse skeletal muscle. Key words: SERCA, sirtuins, acetylation, calcium handling, diabetes, muscle. La calcium ([Ca.sup.2+]) ATPase du reticulum sarco(endo)plasmique (ou SERCA pour << Sarco(endo)plasmic reticulum Calcium ATPase >>) effectue le transport des ions [Ca.sup.2+] dans le muscle. Les perturbations de l&apos;activite de la SERCA pourraient contribuer a la myopathie diabetique. La sirtuine (SIRT) 3 participe a la regulation du metabolisme et du fonctionnement des muscles. Toutefois, on ne sait pas si la SIRT3 participe a l&apos;activite ou a l&apos;acetylation de la SERCA musculaire. Nous avons cherche a etablir que la surexpression de la SIRT3 favorise l&apos;activite de la SERCA dans le muscle gastrocnemien de souris et que la surexpression de la SIRT3 permet de preserver l&apos;activite de la SERCA du muscle gastrocnemien dans un modele de diabete de type 2 engendre par l&apos;administration d&apos;un regime alimentaire a teneur elevee en matieres grasses et en saccharose (HFHS). Nous avons aussi cherche a etablir que le statut d&apos;acetylation de la SERCA en proteines dans le muscle gastrocnemien de souris est altere par la surexpression de la SIRT3 ou le regime alimentaire de type HFHS. Pendant 4 mois, nous avons administre un regime alimentaire de type standard ou HFHS chez des souris de type sauvage (WT) et transgeniques ([SIRT3.sub.TG]), surexprimant la SIRT3 dans le muscle squelettique. Les souris [SIRT3.sub.TG] et WT ont presente de l&apos;obesite et de l&apos;intolerance au glucose apres l&apos;administration d&apos;un regime de type HFHS pendant 4 mois. Le [V.sub.max] de la SERCA etait plus eleve dans le muscle gastrocnemien des souris [SIRT3.sub.TG] que des souris WT. Les souris HFHS presentaient un taux de SERCA1a en proteines et un [V.sub.max] de la SERCA dans le muscle gastrocnemien moins eleves que les souris temoins. La diminution du [V.sub.max] de la SERCA entraoenee dans le muscle gastrocnemien par le regime alimentaire de type HFHS s&apos;attenuait avec la surexpression de la SIRT3 chez les souris [SIRT3.sub.TG] auxquelles etait administre un regime alimentaire de type HFHS. Le genotype ou le regime alimentaire n&apos;entraoenaient pas d&apos;alteration de l&apos;acetylation de la SERCA1a et de la SERCA2a dans le muscle gastrocnemien de souris. Ces resultats laissent entendre que la surexpression de la SIRT3 permettrait d&apos;ameliorer le fonctionnement de la SERCA dans le muscle squelettique de souris. [Traduit par la Redaction] Mots-cles : SERCA, sirtuines, acetylation, manipulation du calcium, diabete, muscle.

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to [...]

The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and [...]

The prevalence of type 2 diabetes (T2D) has increased dramatically over the past two decades, not only among adults but also among adolescents. T2D is a systemic disorder affecting every [...]

The incidence of obesity and type 2 diabetes mellitus have risen across the world during the past few decades and has also reached an alarming level among children. In addition, [...]