Endogenous Pancreatic Enzyme Activity Levels Show no Significant Effect on Human Islet Isolation Yield

Area of Science:

• Endocrinology
• Surgical Research
• Biochemistry

Background:

• Human islet isolation is crucial for type 1 diabetes treatment but faces challenges with inconsistent yields.
• Serine proteases, like trypsin, have been implicated as potentially damaging to islet yield.
• Enzyme activity during isolation needs further investigation to optimize outcomes.

Purpose of the Study:

• To evaluate the impact of serine protease activity on human islet isolation yield and functionality.
• To compare enzyme activity profiles between successful and unsuccessful islet isolations.
• To determine if enzyme inhibitor supplementation affects islet isolation outcomes.

Main Methods:

• Analyzed enzyme activity (trypsin, chymotrypsin, elastase) spectrophotometrically in 42 human islet isolation procedures.
• Classified isolations as successful (n=19) or unsuccessful (n=23) based on islet yield and function.
• Compared enzyme activity profiles and tissue digestion parameters between the two groups.

Main Results:

• No significant differences in donor variables were observed.
• Successful isolations showed significantly greater pancreatic tissue digestion (85.6% vs 74.8%) in shorter times (19.7 min vs 22.6 min).
• Serine protease levels, even with inhibitors, did not significantly affect islet isolation outcomes.

Conclusions:

• Serine protease activity does not appear to be a primary factor limiting human islet yield.
• Maximizing tissue digestion within the shortest time correlates with successful islet isolation.
• Future research should investigate the role of collagenase in the endocrine-exocrine tissue dissociation process.