The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.

This research investigates the role of metalloproteinases, specifically MMP-2, MMP-9, MT1-MMP, ADAMTS-4, and TIMP-3, in the development of insulin-induced laminitis in horses. The findings suggest that, except for MMP-9, these enzymes do not seem to significantly contribute to the disease.

Understanding Metalloproteinases and Laminitis

• Metalloproteinases are enzymes that play a key role in remodeling the extracellular matrix, a function that has linked them to various inflammatory conditions, including laminitis in horses.
• Laminitis is a disease that affects the feet in horses, causing severe pain and disability. While it’s known that some metalloproteinases are more active in horses with laminitis and systemic inflammation, the role of these enzymes in insulin-induced laminitis, which occurs without systemic inflammation, has been unclear.

Methodology of the Study

• The researchers studied the gene expression of several metalloproteinases (MMP-2, MMP-9, MT1-MMP, ADAMTS-4) and an inhibitor (TIMP-3) in the lamellar tissue of horses. Some of the horses were healthy controls, while others were made to develop laminitis by inducing hyperinsulinaemia for 48 hours.
• The protein concentrations of MMP-2 and MMP-9 were evaluated using gelatin zymography at various time-points (6h, 12h, 24h, and 48h) during prolonged hyperinsulinaemia, and in control horses.

Findings of the Study

• The study found only one change in gene expression – an increase in MMP-9 in horses that developed insulin-induced laminitis. The levels of pro MMP-9 also increased during the acute phase of laminitis (48 hours), while pro MMP-2 levels remained similar in all horses.
• Based on these findings, the researchers concluded that MMP-2, MT1-MMP, TIMP-3, and ADAMTS-4 do not seem to significantly contribute to insulin-induced laminitis. The elevated levels of MMP-9 could either be a result of inflammation caused by the infiltration of leukocytes, or a direct result of the hyperinsulinaemia itself.
• However, the exact role of MMP-9 as a possible player in the breakdown of the basement membrane during laminitis is still undefined, as it appeared to be mostly in the inactive form.