Glucose and glucose analogs modulate collagen metabolism

Area of Science:

• Biochemistry
• Cell Biology
• Diabetology

Background:

• Diabetes mellitus is associated with complications in collagen-containing connective tissues.
• Previous research indicates glucose inhibits collagen fibril formation and cross-linking in vitro.
• Reduced collagen cross-linking increases susceptibility to collagenolytic degradation, potentially lowering collagen levels.

Purpose of the Study:

• To investigate the effects of D-glucose and its analogs on collagen metabolism in chick calvaria organ cultures.
• To elucidate the mechanisms underlying decreased collagen levels in diabetic connective tissues.

Main Methods:

• Organ cultures of chick calvaria were treated with D-glucose, L-glucose, and 2-deoxy-D-glucose.
• Parameters of collagen synthesis, fibril formation, cross-linking, and degradation were assessed.
• The role of glucose transport was examined using 2-deoxy-D-glucose.

Main Results:

• All three sugars inhibited collagen fibril formation.
• D-Glucose stimulated collagen synthesis, L-glucose had no effect, and 2-deoxy-D-glucose inhibited synthesis.
• D-Glucose reversed the inhibitory effect of 2-deoxy-D-glucose on synthesis.
• L-glucose and 2-deoxy-D-glucose stimulated collagen degradation, an effect further enhanced when glucose transport was inhibited.

Conclusions:

• Decreased collagen levels in diabetics may result from inhibited collagen fibril formation and cross-linking.
• Increased collagen degradation also contributes to reduced collagen levels in diabetic connective tissues.
• Glucose transport plays a role in regulating collagen degradation.