Smooth Muscle Insulin Receptor Deletion Causes Voiding Dysfunction: A Mechanism for Diabetic Bladder Dysfunction.

Area of Science:

• Urology
• Endocrinology
• Cell Biology

Background:

• Diabetic bladder dysfunction (DBD) is a frequent diabetes complication.
• Myogenic abnormalities are common in DBD, but mechanisms are unclear.
• Smooth muscle insulin receptor (IR) signaling's role in DBD pathogenesis needs investigation.

Purpose of the Study:

• To investigate the role of smooth muscle insulin receptor (IR)-mediated signaling in diabetic bladder dysfunction (DBD).
• To determine the impact of IR deletion in bladder smooth muscle (BSM) on BSM function and voiding phenotypes.

Main Methods:

• Conditional deletion of smooth muscle IR in mice (heterozygous SMIR+/- and homozygous SMIR-/-).
• Assessment of voiding phenotypes, BSM contractility, and bladder morphology.
• Analysis of protein expression (FoxO, mTOR, Chrm3, P2x1, Sm22, Cav1.2, adiponectin) and signaling pathways.

Main Results:

• SMIR+/- and SMIR-/- mice showed abnormal voiding (urinary frequency, small voids) despite normal blood glucose.
• BSM exhibited diminished contraction force, bladder dilation, and disorganized muscle layers.
• IR deletion altered protein expression (increased FoxO, decreased mTOR) and inhibited adiponectin signaling, affecting BSM functional proteins.

Conclusions:

• Disruption of IR-mediated signaling in BSM leads to impaired proliferation and differentiation.
• This results in diminished BSM contractility and voiding dysfunction, recapitulating human DBD.
• Targeting smooth muscle IR signaling may offer therapeutic strategies for diabetic bladder complications.