Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respo Show more
Type 2 diabetes mellitus (T2DM) is a worldwide health problem that has raised major concerns to the public health community. This chronic condition typically results from the cell's inability to respond to normal insulin levels. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the primary incretin hormones secreted from the intestinal tract. While clinical research has extensively explored the therapeutic potential of GLP-1R in addressing various T2DM-related abnormalities, the possibility of GIPR playing an important role in T2DM treatment is still under investigation. Evidence suggests that GIP is involved in the pathophysiology of T2DM. This chapter focuses on examining the role of GIP as a therapeutic molecule in combating T2DM, comparing the past, present, and future scenarios. Our goal is to delve into how GIP may impact pancreatic β-cell function, adipose tissue uptake, and lipid metabolism. Furthermore, we will elucidate the mechanistic functions of GIP and its receptors in relation to other clinical conditions like cardiovascular diseases, non-alcoholic fatty liver diseases, neurodegenerative diseases, and renal disorders. Additionally, this chapter will shed light on the latest advancements in pharmacological management for T2DM, highlighting potential structural modifications of GIP and the repurposing of drugs, while also addressing the challenges involved in bringing GIP-based treatments into clinical practice. Show less
Although fish exposed to municipal wastewater effluents (MWWE) show higher lipid accumulation, whether this is due to adipogenesis is unclear. The objective here was to identify molecular markers of a Show more
Although fish exposed to municipal wastewater effluents (MWWE) show higher lipid accumulation, whether this is due to adipogenesis is unclear. The objective here was to identify molecular markers of adipogenesis in zebrafish (Danio rerio) larvae for use as high throughput screening tools for environmental contaminants, including obesogens in MWWE. Zebrafish larvae were fed a commercial diet at a maintenance level (5 % body mass) or in excess (25 or 50 % body mass) from day 6 to 30 days post-fertilization (dpf) to stimulate adipogenesis. We monitored fat accumulation and markers of lipid metabolism, including peroxisome proliferator-activated receptor γ (ppar γ), fatty acid synthase (fas), ELOVL fatty acid elongase 2 (elovl2), diacylglycerol O-acyltransferase 2 (dgat2), leptin (lepa and lepb), leptin receptor (lepr), and lipoprotein lipase (lpl). Excess feeding led to a higher growth rate, protein content and an increase in igf1 transcript abundance. Also, these larvae had higher triglyceride levels and accumulated lipids droplets in the abdominal cavity and viscera. The molecular markers of adipogenesis, including fas, elovl2, and dgat2, were upregulated, while the transcript abundance of lpl, a lipolytic gene, was transiently lower due to excess feeding. The increased adiposity seen at 30 dpf due to excess feeding coincided with a lower lep but not lepr transcript abundance in zebrafish. Our results demonstrate that excess feeding alters the developmental programming of key genes involved in lipid homeostasis, leading to excess lipid accumulation in zebrafish larvae. Overall, fas, elovl2, lpl, and dgat2, but not lep or ppar γ, have the potential to be biomarkers of adipogenesis in zebrafish larvae. Show less