Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Mar;17(1):25-34.
doi: 10.1007/s12079-022-00680-4. Epub 2022 May 12.

The functions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in diabetes progression

Khaled Benchoula  1 , Ahmed Mediani  2 , Wong Eng Hwa  3
Affiliations
Review

The functions of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in diabetes progression

Khaled Benchoula et al. J Cell Commun Signal. 2023 Mar.

Abstract

The increase in blood glucose causes a myriad of pathways and molecular components to malfunction, leading to diabetes. Diabetes affects each organ differently by activating distinct pathways. It has an impact on the liver, pancreas, kidney (nephropathy), eyes (retinopathy), and nervous system (neuropathy). Understanding the effects of diabetes on each organ is the first step in developing a sustained treatment for the disease. Among the many cellular molecules impacted by diabetes is Ca2+/calmodulin-dependent protein kinase II (CaMKII), a complex Ca2+/calmodulin-activated serine/threonine-protein kinase. When intracellular [Ca2+] rises, it binds to calmodulin (CaM) to produce Ca2+/CaM, which activates CaMKIIs. This factor is involved in the pancreas, liver, heart, muscles, and various organs. Thus, Understanding CaMKII action in each organ is critical for gaining a complete picture of diabetic complications. Therefore, this review covers CaMKII's functions in many organs and how it affects and has been affected by diabetes.

Keywords: CaMKII; Diabetes; Diabetes treatment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
The activation of CAMKII process. Increased concentrations of Ca2+ enhance Ca2+/calmodulin binding to the calmodulin-binding domain of CaMKII. This unmasks the pseudosubstrate domain and causes conformational changes, therefore triggering autophosphorylation at distinct locations
Fig. 2
Fig. 2
The function of CAMKII in regulating the glucose production in the liver via TRB3 and FoxO1. cAMP cyclic adenosine monophosphate, PKA protein kinase A, IP3R inositol 3-phosphate receptors, HDAC1/4 histone deacetylase 1/4, ATF4/6 activating transcription factor 6, PERK PRKR-like endoplasmic reticulum kinase, AKT serine/threonine kinase, FoxO1 forkhead box O1, TRB3: CaMKII Ca2+/CaM-dependent protein kinase II
See this image and copyright information in PMC

References

    1. Bao SL, Pan J, Sun HX, Liu WT. Valsartan improves cardiac function in mice with diabetes mellitus by CaMKII/AngII. Eur Rev Med Pharmacol Sci. 2018;22:5327–5334. - PubMed
    1. Castro AJG, Frederico MJS, Cazarolli LH, et al. The mechanism of action of ursolic acid as insulin secretagogue and insulinomimetic is mediated by cross-talk between calcium and kinases to regulate glucose balance. Biochim Biophys Acta. 2015;1850:51–61. doi: 10.1016/j.bbagen.2014.10.001. - DOI - PubMed
    1. Chen Y, Hua Y, Li X, et al. Distinct types of cell death and the implication in diabetic cardiomyopathy. Front Pharmacol. 2020;11:42. doi: 10.3389/fphar.2020.00042. - DOI - PMC - PubMed
    1. Chen J, Fleming T, Katz S, et al. CaM kinase II-δ is required for diabetic hyperglycemia and retinopathy but not nephropathy. Diabetes. 2021;70:616–626. doi: 10.2337/db19-0659. - DOI - PubMed
    1. Chou C, Ho C, Lee H, et al. Roles of impaired intracellular calcium cycling in arrhythmogenicity of diabetic mouse model. Pacing Clin Electrophysiol. 2017;40:1087–1095. doi: 10.1111/pace.13166. - DOI - PubMed