Adenosine monophosphate- activated protein kinase- based classification of diabetes pharmacotherapy.

The article named “Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy” by Dutta et al.[1] published in your journal has enlightened us about the role of adenosine monophosphate-activated protein kinase (AMPK) in pathogenesis and the management of diabetes mellitus. In this article, the interaction between sodium-glucose cotransporter type 1 (SGLT1) and AMPK has also been mentioned.[1] The presence of SGLT1 receptors on human as well as “murine Langendorff perfused hearts” has been well supported by an animal study.2 This study has also demonstrated that SGLT1 inhibitors may also contribute to the increased risk of ischemia–reperfusion injury of the myocardium. SGLT1 is a high-affinity, low-capacity transporter. For this reason, SGLT1 may have a cardioprotective effect on myocardium during ischemia. It is helpful particularly when the availability of fuel is less.[2] We know that nowadays, SGLT2 inhibitors are emerging as newer antidiabetic drugs. Apart from their glucose lowering effects, they have significant effects on other metabolisms also.[3] The authors have rightly mentioned that link between SGLT1 and AMPK at brain and heart has suggested the urgent need for studies evaluating the link between SGLT2 and AMPK.[1] In this regard, we can see that a recent study has compared the expression of SGLT1 and SGLT2 in human myocardium with either ischemia or hypertrophy. Healthy subjects are taken as control. No expression of SGLT2, at both gene and protein level, in either healthy or ischemic/hypertrophic myocardium has been found. In ischemic/hypertrophic myocardium, phosphorylation/activation of AMPK was also increased along with expression of SGLT1. However, the study could not demonstrate a causative association with SGLT1 upregulation and activation of AMPK. Interestingly, experimental cardiomyopathy induced by a hyperactivating mutation of AMPK in mice is associated with increased expression of SGLT1.[4] Another recent data reveal that cardiotrophin-1 inhibits intestinal sugar absorption by SGLT-1 level reduction. The AMPK pathway contributes to this effect. This finding may explore new targets for therapy in future.[5]

These molecular pathways are still to be clarified and to be made clearer by further studies. We would like to thank the authors of the article mentioned above to highlight these points regarding the role of AMPK. We know that the role of SGLT2 inhibitors on cardiovascular morbidities in diabetic patients is an emerging topic of discussion now. Some of these drugs have some action on the SGLT1 receptors also.[4] We will be glad if we can get the authors’ opinion regarding the role of the “gliflozins” drugs in this regard. Can these drugs play a role in this SGLT-AMPK interaction and alter the cardiovascular outcomes?

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