Impaired glycogen synthase activating system in human diabetic polymorphonuclear leukocytes

Area of Science:

• Biochemistry
• Cell Biology
• Endocrinology

Background:

• Diabetes mellitus is a metabolic disorder affecting glucose regulation.
• Glycogen synthase is a key enzyme in glycogen synthesis.
• Polymorphonuclear leukocytes (PMN) play roles in inflammation and immune response.

Purpose of the Study:

• To investigate the impact of diabetes mellitus on glycogen synthase activity and its regulatory system in human PMN.
• To determine if diabetes affects the conversion of inactive glycogen synthase (synthase-D) to its active form (synthase-l).
• To differentiate between defects in the synthase enzyme and its activating phosphatase in diabetic PMN.

Main Methods:

• Human PMN were isolated from healthy and diabetic individuals using gradient sedimentation.
• Enzyme activities of endogenous and total glycogen synthase were measured.
• The conversion rate of synthase-D to synthase-l and maximum synthase-l attained were assessed in cell homogenates.
• Synthase phosphatase activity was measured using both endogenous and purified synthase-D substrates.

Main Results:

• No significant differences were found in endogenous and total glycogen synthase activities between diabetic and control PMN.
• The conversion of synthase-D to synthase-l and the maximum percentage of synthase-l were reduced in diabetic PMN homogenates.
• No correlation was observed between plasma glucose levels and the rate of synthase-D to synthase-l conversion.
• Glycogen synthase phosphatase activities did not differ between control and diabetic cells under experimental conditions.

Conclusions:

• Diabetes mellitus induces a defect in the conversion of endogenous glycogen synthase-D to synthase-l within PMN.
• This defect is localized at the level of the glycogen synthase enzyme itself.
• The activating synthase phosphatase system does not appear to be impaired in diabetic PMN, suggesting a primary enzyme dysfunction.