The AMPK system is present in different kinds of cells and is an important intracellular energy sensor. AMPK has also an inhibitory site at Ser485 of the α1 subunit. The binding of both AMP and ADP to the γ-subunit is competitively inhibited by ATP, which indicates that AMPK is a sensor of AMP/ATP or ADP/ATP ratios. The activation of AMPK is due to an increase in the intracellular AMP:ATP ratio and phosphorylation of Thr172 on the activation loop of the α-subunit. Each subunit possesses also isoforms (α1, α2, β1, β2, γ1, γ2, γ3), making a total of 12 possible heterotrimer combinations. AMPK occurs as a heterotrimer, consisting of a catalytic α-subunit and regulatory β- and γ-subunits. However, more studies are required to better elucidate the relevance of AMPK in the (patho)physiology of the insulin-secreting cells.Īdenosine monophosphate-activated protein kinase (AMPK, EC 2.7.11.31) belongs to the family of serine/threonine kinases. These data suggest that AMPK may be a target for compounds improving the functionality of β cells. Moreover, studies with animal models demonstrated impaired link between glucose and AMPK activity in pancreatic islet cells. It was shown that in pancreatic islets of humans with type 2 diabetes, AMPK is downregulated. AMPK is also involved in the regulation of gene expression and may protect β cells against glucolipotoxic conditions. This effect is primarily due to increased intracellular calcium concentrations. However, pharmacological activation of AMPK significantly potentiates the insulin-secretory response of β cells to glucose and to some other stimuli.
Results of in vitro studies clearly show that glucose-induced insulin release is associated with a concomitant inhibition of AMPK in β cells. AMPK is also expressed in pancreatic β cells and is largely regulated by glucose, which is the main physiological stimulator of insulin secretion. Upon activation, AMPK affects metabolic pathways leading to increased formation of ATP and simultaneously reducing ATP-consuming processes. AMPK is activated, among others, in response to glucose deprivation, caloric restriction and increased physical activity. AMPK is an important intracellular energy sensor and plays a relevant role in whole-body energy homeostasis. AMP-activated protein kinase (AMPK) is present in different kinds of metabolically active cells.
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