**9. Glucose metabolism**

Glucose activates other cell signals, such as cyclic AMP (cAMP), cyclic GMP (cGMP), inositol 1,4,5-trisphosphate (IP3), and diacylglycerol (DAG). When cAMP is produced, it then activates protein kinase A (PKA). cAMP may be the most crucial molecule that leads to insulin secretion and phosphorylation of proteins involved in insulin exocytosis via PKA. Incretin hormones also augment glucose-stimulated insulin secretion by stimulating the cAMP signaling pathway [8].

Incretin hormones are gut peptides secreted by enteroendocrine cells after feeding [21]; their function is to control the amount of insulin. In the pancreas, two kinds of incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), share the same behavior, but outside the pancreas, they differ. They are both rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A decrease in incretin secretion or an increase in incretin clearance is not a pathogenic factor in DM. However, in T2D, GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels. GIP incompetence is detrimental to β-cell function, especially after eating. On the other hand, GLP-1 is still insulinotropic in T2D, which has led to the production of compounds that activate the GLP-1 receptor intending to improve insulin secretion [22].

Furthermore, glucose metabolism is critical in insulin biosynthesis because it triggers insulin gene transcription and mRNA translation. The triggering of insulin gene transcription and mRNA translation is necessary for regulating insulin biosynthesis via modification of proinsulin mRNA expression and maintaining insulin mRNA stability [8]. mRNA has a vital role in regulating and controlling gene expression and this stability is affected by how RNA-binding proteins and structural elements interact with each other.

Regulation of mRNA stability is accomplished through various reactions to developmental stimuli (e.g., nutrient levels, cytokines, hormones, and temperature shifts or to different environmental stimuli such as stresses like hypoxia, hypocalcemia, viral infection, and tissue injury). However, deregulated mRNA stability can cause mRNA accumulation contributing to some forms of neoplasia, thalassemia, and AD [23]. The results from *in vitro* studies revealed that insulin mRNA stability decreases under lower glucose concentrations and increases under high glucose conditions [8]. In the absence of glucose, insulin mRNA levels in β-cells decrease sharply, which is reversed by elevating intracellular cAMP levels.
