There is a growing interest in possible links between impaired insulin signaling and the pathogenesis of Alzheimer's disease. Insulin and insulin-signaling mechanisms are important for neuronal survival, and central nervous system neurodegeneration is associated with dysfunctional neuronal insulin receptors. This short review focuses on recent findings that many important components of Alzheimer's disease appear to stem from imbalances in insulin signaling intrinsic to the brain, rather than systemic insulin imbalances, and that treatments aimed at redressing insulin imbalances in the brain could be effective therapies.
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http://dx.doi.org/10.1358/dot.2006.42.12.1032059 | DOI Listing |
Diabetes
January 2025
Department of Geriatrics, Peking University Shenzhen Hospital, Shenzhen, China.
Insulin resistance, a hallmark of type 2 diabetes, accelerates muscle breakdown and impairs energy metabolism. However, the role of Ubiquitin Specific Peptidase 2 (USP2), a key regulator of insulin resistance, in sarcopenia remains unclear. Peroxisome proliferator activated receptor γ (PPARγ) plays a critical role in regulating muscle atrophy.
View Article and Find Full Text PDFGenetics
January 2025
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation.
View Article and Find Full Text PDFPLoS Biol
January 2025
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) CCT UNS-CONICET, Bahía Blanca, Argentina.
The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood.
View Article and Find Full Text PDFClin Sci (Lond)
January 2025
Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.
View Article and Find Full Text PDFLife Metab
December 2024
Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China.
Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss.
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