Insulin reversal of alloxan–diabetes induced changes in gingival collagen metabolism of the rat

Abstract

Adult, male Sprague‐Dawley rats were randomly divided into the following groups: control, control + insulin, alloxan‐diabetic, and diabetic + insulin. Diabetes was induced by a single dose of alloxan (200 mg/Kg body weight), administered i.p. in isotonic saline. Rats in the control + insulin group received 3 I.U. of insulin daily. The diabetic + insulin group were given sufficient insulin (3–5 I.U.) to maintain their urine glucose levels in a 0‐1/4 % range. Urinary glucose levels for each animal were determined daily. The animals were killed after 21 days and the fasting blood glucose concentration, serum and 24 hour urinary levels of hydroxyproline, gingival collagen and protein concentrations were determined. Collagenolytic activity of rat gingivae in tissue culture was also measured. The alloxan‐diabetic rats showed (1) a marked hyperglycemia and glycosuria, (2) decreased levels of water‐soluble protein and acid‐soluble collagen in gingivae, (3) an increased collagenase activity of gingival fragments in culture and (4) a marked increase in the serum concentration and urinary excretion of hydroxyproline. The administration of insulin to the diabetic rats partially or completely returned to normal levels each of the altered physiological parameters described above. These insulin sensitive changes appear, therefore, to have resulted from the diabetic condition of the rats rather than from any non‐diabetic effects of alloxan treatment. Similar changes in gingival collagen metabolism in humans, if present, could be related to the more rapid periodontal destruction observed in diabetic patients.

Tetracyclines Inhibit Connective Tissue Breakdown: New Therapeutic Implications for an Old Family of Drugs

“…Golub and co-workers were examining the alterations in host response, specifically abnormalities in gingival collagen metabolism, that might promote the unusually aggressive periodontal breakdown often associated with the poorly controlled diabetic state. [18][19][20][21] They also proposed that the diabetic rat could serve as a clinically relevant model to study a variety of host factors that might contribute to accelerated periodontal tissue breakdown in general. An early example, using this approach, was their unexpected finding that inducing diabetes in the rat suppressed (rather than enhanced) the loss of collagen during experimentally induced inflammation in the gingiva.20 '22 One explanation was that diabetes suppressed the activity (e.g., chemotactic, phagocytic) of polymorphonuclear leukocytes (PMNs), initially preventing collagen breakdown by this tissue-destructive cell but ultimately, with time, leading to unusually severe periodontal disease because of the cell's primary host-defense function.…”

“…McCulloch et al* administered a regular dose of doxycycline (100 mg/d) to 29 "high risk", "recurrent periodontitis" adult patients in a double-blind, 1-year clinical trial; 19 patients were administered a placebo. The authors reported that doxycycline significantly reduced the risk of "recurrent active periodontitis," an effect that was observed 7 months after the 3 week-regimen of the drug.…”

Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease

“…The production of collagen and glycosaminoglycans is significantly reduced in high-glucose environments. [91] In diabetic patients, proteins become glycated to form advanced glycation end products (AGE). [9192] The formation of AGE begins when glucose attaches to the amino groups on proteins to form an unstable glycated protein (Schiff base).…”

Diabetes, periodontitis, and the subgingival microbiota

“…Collagenases are known to be increased in the periodontium of diabetics (47). These increases in collagenases may be reversed with good glycaemic control (48). …”