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

Abstract

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future.

Is Metformin a Treatment Opportunity for Colorectal Cancer?

“…(46) Metformin activates the AMPK pathway in normal and cancer cells. Studies in animal models show that metformin induces AMPK signalling cascade and inhibits tumour growth and colon tumour formation, (21,23,47) and also studies in cell lines have reported that metformin reduces cell proliferation in colon cancer by AMPK activation. (48) Metformin treatment also activated AMPK regulates β-catenin to decrease cell proliferation in human colon carcinoma RKO cells.…”

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

“…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.…”

“…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.…”

“…[ 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.…”

Váro-centric Diabetes Management

“…This classification is based upon phenotype, and is backed by insights from pathophysiology, biochemistry and endocrinology. 6,7 A type 2 diabetes person in catabolism will have predominant insulin deficiency, with a low insulin/glucagon ratio, and AMP-activated protein kinase (AMPK) hyperactivity. A maladaptive anabolic individual, on the other hand, will be predominantly insulin resistant, have a high insulin/glucagon ratio, and require AMPK activation.…”