Disruption of Hepatic Mitochondrial Pyruvate and Amino Acid Metabolism Impairs Gluconeogenesis and Endurance Exercise Capacity in Mice
Am J Physiol Endocrinol Metab. 2024 Feb 14. doi: 10.1152/ajpendo.00258.2023. Online ahead of print.ABSTRACTExercise robustly increases the glucose demands of skeletal muscle. This demand is met not only by muscle glycogenolysis, but also by accelerated liver glucose production from hepatic glycogenolysis and gluconeogenesis to fuel mechanical work and prevent hypoglycemia during exercise. Hepatic gluconeogenesis during exercise is dependent on highly coordinated responses within and between muscle and liver. Specifically, exercise increases the rate at which gluconeogenic precursors such as pyruvate/lactate or amino acids ...
Source: American Journal of Physiology. Endocrinology and Metabolism - February 14, 2024 Category: Physiology Authors: Michael R Martino Mohammad Habibi Daniel Ferguson Rita T Brookheart John P Thyfault Gretchen A Meyer Louise Lantier Curtis C Hughey Brian N Finck Source Type: research

Increasing maternal glucose concentrations is insufficient to restore placental glucose transfer in chorionic somatomammotropin RNA interference pregnancies
Am J Physiol Endocrinol Metab. 2024 Feb 14. doi: 10.1152/ajpendo.00331.2023. Online ahead of print.ABSTRACTWe previously demonstrated impaired placental nutrient transfer in chorionic somatomammotropin (CSH) RNA interference (RNAi) pregnancies, with glucose transfer being the most impacted. Thus, we hypothesized that despite experimentally elevating maternal glucose, diminished umbilical glucose uptake would persist in CSH RNAi pregnancies, demonstrating the necessity of CSH for adequate placental glucose transfer. Trophectoderm of sheep blastocysts (9 days of gestational age; dGA) were infected with a lentivirus expressin...
Source: American Journal of Physiology. Endocrinology and Metabolism - February 14, 2024 Category: Physiology Authors: Amelia R Tanner Victoria C Kennedy Cameron S Lynch Quinton A Winger Russell V Anthony Paul J Rozance Source Type: research

Corrigendum for Stamateris et al., volume 305, 2013, p. E149-E159
Am J Physiol Endocrinol Metab. 2024 Feb 1;326(2):E148. doi: 10.1152/ajpendo.00040.2023_COR.NO ABSTRACTPMID:38329433 | DOI:10.1152/ajpendo.00040.2023_COR (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - February 8, 2024 Category: Physiology Source Type: research

Vitamin D promotes the folate transport and metabolism in zebrafish ( < em > Danio rerio < /em > )
Am J Physiol Endocrinol Metab. 2024 Feb 7. doi: 10.1152/ajpendo.00380.2023. Online ahead of print.ABSTRACTVitamin D(VD) is a fat-soluble sterol that possesses a wide range of physiological functions. The present study aimed to evaluate the effects of VD on folate metabolism in zebrafish and further investigate the underlying mechanism. Wild-type (WT) zebrafish were fed with the diet containing 0 IU/kg VD3 or 800 IU/kg VD3 for 3 weeks. Meanwhile, cyp2r1 mutant zebrafish with impaired VD metabolism served as another model of VD deficiency. Our results showed that VD deficiency in zebrafish suppressed the gene expression of f...
Source: American Journal of Physiology. Endocrinology and Metabolism - February 7, 2024 Category: Physiology Authors: Shufei Liang Hui Zhang Lin Jiao Rui Shao Yawen Lan Xinmeng Liao Kangsen Mai QingHui Ai Min Wan Source Type: research

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog
This study characterized the time course of glucagon-mediated molecular events and their relevance to metabolic flux in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a 6-fold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group glucose remained at basal, while in the other, glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) and largely sustained increase in hepatic cAMP over 4h, a continued elevation in glucose-...
Source: American Journal of Physiology. Endocrinology and Metabolism - February 7, 2024 Category: Physiology Authors: Katie C Coate Christopher J Ramnanan Marta Smith Jason J Winnick Guillaume Kraft Jose Irimia-Dominguez Ben Farmer E Patrick Donahue Peter J Roach Alan D Cherrington Dale S Edgerton Source Type: research

Effects of exogenous lactate on lipid, protein, and glucose metabolism - a randomized cross-over trial in healthy males
Conclusion: Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole-body phenylalanine flux was increased. Clinical trial registrations: NCT04710875.PMID:38324259 | DOI:10.1152/ajpendo.00301.2023 (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - February 7, 2024 Category: Physiology Authors: Mette Gb Pedersen Nikolaj Rittig Maj Bangshaab Kristoffer Berg-Hansen Nigopan Gopalasingam Lars C Gormsen Esben S øndergaard Niels M øller Source Type: research

Effect of resveratrol on insulin action in primary myotubes from lean and individuals with severe obesity
Conclusions. AMPK phosphorylation may play an indispensable role in improving glucose metabolism following resveratrol treatment and may be able to overcome intrinsic deficits in the insulin signaling cascade in myotubes from individuals with severe obesity.PMID:38324260 | DOI:10.1152/ajpendo.00299.2023 (Source: American Journal of Physiology. Endocrinology and Metabolism)
Source: American Journal of Physiology. Endocrinology and Metabolism - February 7, 2024 Category: Physiology Authors: Sanghee Park Filip Jevtovic Polina M Krassovskaia Alec B Chaves Donghai Zheng Jonas T Treebak Joseph A Houmard Source Type: research

Quantification of the Immunometabolite Protein Modifications S-2-Succinocysteine and 2,3- Dicarboxypropylcysteine
Am J Physiol Endocrinol Metab. 2024 Feb 7. doi: 10.1152/ajpendo.00354.2023. Online ahead of print.ABSTRACTThe tricarboxylic acid (TCA) cycle metabolite fumarate non-enzymatically reacts with the amino acid cysteine to form S-(2-succino)cysteine (2SC), referred to as protein succination. The immunometabolite itaconate accumulates during lipopolysaccharide (LPS) stimulation of macrophages and microglia. Itaconate non-enzymatically reacts with cysteine residues to generate 2,3-dicarboxypropylcysteine (2,3-DCP), referred to as protein dicarboxypropylation. Since fumarate and itaconate levels dynamically change in activated imm...
Source: American Journal of Physiology. Endocrinology and Metabolism - February 7, 2024 Category: Physiology Authors: J Hunter Cox Richard S McCain Emery Tran Shoba Swaminathan Holland H Smith Gerardo G Piroli Michael Shtutman Michael D Walla William E Cotham Norma Frizzell Source Type: research

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice
This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to th...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 31, 2024 Category: Physiology Authors: Minoru Tanaka Ken Sugimoto Hiroshi Akasaka Shino Yoshida Toshimasa Takahashi Taku Fujimoto Keyu Xie Yukiko Yasunobe Koichi Yamamoto Takumi Hirabayashi Ryosuke Nakanishi Hidemi Fujino Hiromi Rakugi Source Type: research

Thiazolidinedione enhances the efficacy of immunotherapy in murine melanoma
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00346.2023. Online ahead of print.ABSTRACTSeveral clinical studies observed a surprising beneficial effect of obesity to increase immunotherapy responsiveness in melanoma patients, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug used to treat diabetes by sequestering fatty acids in the metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-Programmed Cell Death Protein 1 (PD-1) treatment in YUMMER1.7 tumor-bear...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 31, 2024 Category: Physiology Authors: Xinyi Zhang Yuan Gao Keyun Tang Zongyu Li Alexandra A Halberstam Liqun Zhou Rachel J Perry Source Type: research

Metabolic underpinnings of cancer-related fatigue
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00378.2023. Online ahead of print.ABSTRACTCancer-related fatigue (CRF) is one of the most prevalent and detrimental complications of cancer. Emerging evidence suggests that obesity and insulin resistance are associated with CRF occurrence and severity in cancer patients and survivors. In this narrative review, we analyzed recent studies including both preclinical and clinical research on the relationship between obesity and/or insulin resistance and CRF. We also describe potential mechanisms for these relationships, though with the caveat that because the mec...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 31, 2024 Category: Physiology Authors: Xinyi Zhang Rachel J Perry Source Type: research

Chronic cortisol-stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain
Am J Physiol Endocrinol Metab. 2024 Jan 31. doi: 10.1152/ajpendo.00410.2023. Online ahead of print.ABSTRACTThe hypothalamus is a key integrating centre that is involved in the initiation of the corticosteroid stress response, and in regulating nutrient homeostasis. While cortisol, the principal glucocorticoid in humans and teleosts, plays a central role in the feeding regulation, the mechanisms are far from clear. We tested the hypothesis that the metabolic changes to cortisol exposure signal an energy excess in the hypothalamus, leading to feeding suppression during stress in fish. Rainbow trout (Oncorhynchus mykiss) were...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 31, 2024 Category: Physiology Authors: Ayelen M Blanco Femilarani Antomagesh Sara Comesa ña Jose L Soengas Mathilakath M Vijayan Source Type: research

Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function
In this report, we examined pH regulation of the Golgi and identified a partial alkalinization of the Golgi lumen in a diabetes model. To further explore this, we generated a β-cell specific knockout (KO) of the v0a2 subunit of the v-ATPase pump, which anchors the v-ATPase to the Golgi membrane. Although loss of v0a2 partially neutralized Golgi pH and was accompanied by distension of the Golgi cisternae, proinsulin export from the Golgi and insulin granule formation were not affected. Furthermore, β-cell function was well preserved. β-cell v0a2 KO mice exhibited normal glucose tolerance in both sexes, no genotypic diffe...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 24, 2024 Category: Physiology Authors: Cierra K Boyer Sandra E Blom Ashleigh E Machado Kristen E Rohli Michelle E Maxson Samuel B Stephens Source Type: research

The Impact of Glucagon to Support Post-Absorptive Glucose Flux and Glycemia in Healthy Rats and its Attenuation in Male Zucker Diabetic Fatty Rats
Am J Physiol Endocrinol Metab. 2024 Jan 24. doi: 10.1152/ajpendo.00192.2023. Online ahead of print.ABSTRACTHyperglucagonemia is a hallmark of type 2 diabetes (T2DM), yet the role of elevated plasma glucagon (P-GCG) to promote excessive post-absorptive glucose production and contribute to hyperglycemia in patients with this disease remains debatable. We investigated the acute action of P-GCG to safeguard/support post-absorptive endogenous glucose production (EGP) and euglycemia in healthy Zucker control lean (ZCL) rats. Using male Zucker diabetic fatty (ZDF) rats that exhibit the typical metabolic disorders of human T2DM, s...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 24, 2024 Category: Physiology Authors: Shanea K Estes Chiyo Shiota Tracy P O'Brien Richard L Printz Masakazu Shiota Source Type: research

Heme-based oxygen gasoreceptors
Am J Physiol Endocrinol Metab. 2024 Feb 1;326(2):E178-E181. doi: 10.1152/ajpendo.00004.2024. Epub 2024 Jan 17.ABSTRACTTo investigate gasocrine signaling, there is a critical need to identify gasoreceptors for the essential gasotransmitters like O2. Based on existing scientific literature, I propose that heme-based O2 sensors, featuring diverse signaling domains across genera, should be explicitly designated as O2 gasoreceptors. Acknowledging that O2 gasoreceptors are likely to belong to multiple protein classes with diverse signaling domains and pathways will facilitate a comprehensive search for O2 gasoreceptors in all or...
Source: American Journal of Physiology. Endocrinology and Metabolism - January 17, 2024 Category: Physiology Authors: Savani Anbalagan Source Type: research