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CAMKK1 in Obesity and Type 2 Diabetes Mellitus: Evidence of Interaction With Appetite-Regulating, Metabolic and

Livio Tarchi1, Lorenzo Bonacchi1, Andrea Di Santo2

  • 1Department of Health Sciences-Center for Integrated Translational Research and Knowledge Transfer (INCLINE), University of Florence, Florence, Italy.

Endocrinology, Diabetes & Metabolism
|September 18, 2025
PubMed
Abstract

Insights

Calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1) is elevated in type 2 diabetes mellitus (T2DM). This study investigated CAMKK1

Area of Science:

  • Metabolic Regulation
  • Endocrinology
  • Biochemistry

Background:

  • Calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1) is a key regulator of energy homeostasis via AMP-activated protein kinase (AMPK).
  • While CAMKK1 is linked to appetite and satiety, its specific role in obesity and type 2 diabetes mellitus (T2DM) is not well understood.
  • This study aimed to determine if CAMKK1 levels are elevated in individuals with diabetes and explore its molecular associations.

Purpose of the Study:

  • To confirm elevated serum levels of CAMKK1 in patients with T2DM compared to obese individuals and controls.
  • To investigate the molecular correlates of CAMKK1, including its associations with AMPK, TNFα, leptin, and ghrelin.
  • To explore the interaction between CAMKK1 and other factors in different diagnostic groups.

Main Methods:

  • Cross-sectional study analyzing serum CAMKK1 levels in 3,061 individuals with obesity, 4,910 patients with T2DM, and 44,257 controls.
  • Age, BMI, and sex-adjusted ANCOVA was used for comparisons.
  • Pearson correlation, linear regression, and mixed graphical models were employed to assess associations and interactions.

Main Results:

  • CAMKK1 serum levels were significantly higher in T2DM patients compared to both obese individuals and controls.
  • Positive associations were found between CAMKK1 and AMPK and TNFα across all groups.
  • Leptin and ghrelin showed positive associations with CAMKK1 only in controls, with disrupted interactions observed in T2DM patients.

Conclusions:

  • Elevated CAMKK1 levels are associated with T2DM, suggesting a potential role in the pathophysiology of the disease.
  • CAMKK1's interplay with inflammatory pathways, such as TNFα, warrants further investigation.
  • These findings offer new insights into CAMKK1's role in metabolic disorders like obesity and T2DM.
Keywords:
calcium/calmodulin‐dependent protein kinaseenergy homeostasisinflammationmetabolic regulationoverweight

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