KCNK16 Deficiency Deteriorates Body Growth and Diet-Independently Decreases Lipid Accumulation in Mice.

BACKGROUND

The potassium channel KCNK16 (TALK-1) is highly expressed in murine and human pancreas and has been implicated in regulating β-cell electrical excitability and glucose-stimulated insulin secretion (GSIS). Genetic studies have linked KCNK16 variants to type 2 diabetes (T2D), yet its physiological role in vivo remains largely unexplored. We aimed to characterize the cardiometabolic functions of KCNK16 in mice.

METHODS

Male constitutive Kcnk16-deficient mice (KCNK16-/-) were characterized on standard (STD) or high-fat diet (HFD) for up to 21 weeks. Phenotyping included measurements of body weight and composition, echocardiography, blood pressure, and indirect calorimetry. Insulin and glucose homeostasis were assessed by tolerance tests and glucose clamp studies.

RESULTS

KCNK16-/- mice showed lower weight gain, less fat and lean mass, reduced diet intake, and shorter body length across diets. Glucose tolerance, insulin sensitivity, hepatic lipid content, and cardiac function remained largely unaffected, except for lower systolic blood pressure under STD. During HFD, KCNK16-/- mice exhibited increased energy expenditure but attenuated first-phase insulin secretion. Pancreatic insulin content was elevated while circulating IGF-1 was diminished.

CONCLUSION

Kcnk16 deficiency reduced somatic growth and body weight and altered energy expenditure, accompanied by modest changes in insulin secretion dynamics, while glucose homeostasis remained preserved.