Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

Abstract

Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.

Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation

“…The meal-induced peak of plasma glucose appears, hence, as an absorption-independent result of a neuronal reflex mechanism to nutrient ingestion involving mainly acute activation of hepatic glucose production [ 120 ]. The physiological significance of such mechanisms may be the anticipation of carbohydrate absorption extracted from nutrients and their storage as glycogen in the liver [ 121 ].…”

Hypoglycemic Effect of Two Mexican Medicinal Plants

“…Particularly, we detected the use of the aerial part of E. longifolium and the rhizome of A. firma to control the disease among healers and T2D patients in the municipalities of Tlanchinol and Huejutla, in the state of Hidalgo. For this purpose, an infusion is prepared and consumed over the day, mainly in the postabsorptive state, where glucose production by the liver plays a crucial role in maintaining blood glucose levels [24]. Our findings suggest that the hypoglycemic effect exerted in vivo by E. longifolium and A. firma could be correlated with the regulation of hepatic glucose output since both plants were able to inhibit two of the key enzymes that participate in gluconeogenesis: G6Pase and FBPase.…”

Approaches to Decrease Hyperglycemia by Targeting Impaired Hepatic Glucose Homeostasis Using Medicinal Plants

“…Afterwards, the enzyme P13K is recruited and activated by IRS to convert phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane to phosphatidylinositol 3,4,5-triphosphate (PIP3), which facilitates the phosphorylation and activation of Akt at two important sites: by phosphoinositide-dependent kinase 1 (PDK1) at residue Thr308 of the catalytic domain, and by mammalian target rapamycin complex 2 (mTORC2) at residue Ser473 of the regulatory domain ( Schultze et al, 2012 ). Specifically in liver, the activated Akt enzyme is responsible for phosphorylating different factors that are involved in the regulation of processes such as glycogen synthesis, gluconeogenesis, and glycogenolysis, which are activated or inhibited under different nutritional circumstances ( Dimitriadis et al, 2021 ).…”