Denervation rapidly induces insulin resistance (i.e., impairments in insulin-stimulated glucose uptake and signaling proteins) in skeletal muscle. Surprisingly, whether this metabolic derangement is long-lasting is presently not clear. The main goal of this study was to determine if insulin resistance is sustained in both oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles following long-term (28 days) denervation. Mouse hindlimb muscles were denervated via unilateral sciatic nerve resection. Both soleus and EDL muscles atrophied ~40%. Strikingly, while denervation impaired submaximal insulin-stimulated [H]-2-deoxyglucose uptake ~30% in the soleus, it enhanced submaximal (~120%) and maximal (~160%) insulin-stimulated glucose uptake in the EDL. To assess possible mechanism(s), immunoblots were performed. Denervation did not consistently alter insulin signaling (e.g., p-Akt (Thr308):Akt; p-TBC1D1 [phospho-Akt substrate (PAS)]:TBC1D1; or p-TBC1D4 (PAS):TBC1D4) in either muscle. However, denervation decreased glucose transporter 4 (GLUT4) levels ~65% in the soleus but increased them ~90% in the EDL. To assess the contribution of GLUT4 to the enhanced EDL muscle glucose uptake, muscle-specific GLUT4 knockout mice were examined. Loss of GLUT4 prevented the denervation-induced increase in insulin-stimulated glucose uptake. In conclusion, the denervation results sustained insulin resistance in the soleus but enhanced insulin sensitivity in the EDL due to increased GLUT4 protein levels.
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http://dx.doi.org/10.3390/ijms22094913 | DOI Listing |
Cardiovasc Diabetol
January 2025
Medical Big Data Center, Department of General Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, No. 26 Daoqian Street, Suzhou, 215001, Jiangsu, China.
Background: Triglyceride-glucose (TyG) related indices, which serve as simple markers for insulin resistance, have been closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease (CVD), and mortality. However, the prognostic utility of TyG-related indices in predicting the risk of CVD and mortality among patients with MASLD remains unclear.
Methods: Data of 97,331 MASLD patients, with a median age of 58.
Cardiovasc Diabetol
January 2025
Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Background: Insulin resistance proxy indicators are significantly associated with cardiovascular disease (CVD) and diabetes. However, the correlations between the estimated glucose disposal rate (eGDR) index and CVD and its subtypes have yet to be thoroughly researched.
Methods: 10,690 respondents with diabetes and prediabetes from the NHANES 1999-2016 were enrolled in the study.
Cardiovasc Diabetol
January 2025
Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari "Rodolfo Paoletti", Università degli Studi di Milano, Milano, Italy.
Background: The triglyceride-glucose (TyG) index is now widely recognized as a marker of insulin resistance and has been linked to the development and prognosis of atherosclerotic cardiovascular diseases (ASCVD) in numerous populations, particularly in the Eastern world. Although there are fewer reports from the Western world, and they are sometimes contradictory, the absence of definitive data on the relationship between a raised TyG index and cardiovascular risk suggested the opportunity of testing this biochemical marker against a well-established vascular marker such as the carotid intima media thickness (c-IMT).
Methods: Primary prevention patients were selected from a cohort of individuals who underwent c-IMT measurement between 1984 and 2018 at the Dyslipidemia Center at the ASST Grande Ospedale Metropolitano Niguarda in Milan, Italy.
BMC Public Health
January 2025
Department of Hepatobiliary Surgery, Second Hospital Affiliated to Chongqing Medical University, Chongqing, P. R. China.
Background: As the global epidemic of obesity fuels metabolic conditions, the burden of nonalcoholic fatty liver disease (NAFLD) will become enormous. Abundant studies revealed the association between high body mass index (BMI) and NAFLD but overlooked the BMI patterns across life stages. We aimed to explore how BMI trajectories over age relate to NAFLD.
View Article and Find Full Text PDFProbiotics Antimicrob Proteins
January 2025
Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine, Udayana University, Denpasar, Bali, 80232, Indonesia.
The absence of suitable intervention significantly increases the likelihood of type 2 diabetes mellitus (T2DM) development in people with prediabetes. Recent statistical findings indicate that the gut microbiome might influences the development of insulin resistance. The objective of our study was to assess the efficacy and safety of probiotic supplementation in individuals diagnosed with prediabetes.
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