Characteristics of research-focused human islet preparations from organ donors with type 2 diabetes

Islets. 2023 Dec 31;15(1):2219104. doi: 10.1080/19382014.2023.2219104.

Abstract

Type 2 diabetes mellitus (T2D) affects 463 million individuals worldwide. β-cell dysfunction and relatively inadequate β-cell mass has been implicated in the pathogenesis of T2D. Primary human islets from T2D patients can reveal the islet dysfunction and the underlying mechanisms and thus have become valued resources for diabetes research. Our center (Human Islet Resource Center, China) has prepared a number of batches of human islets from T2D organ donors. The present study aims to characterize islet isolation processes, islet yields, and qualities of T2D pancreases by comparing with non-diabetic (ND) ones. Overall, 24 T2D and 80 ND pancreases were obtained with informed research consents. The digestion time, islet purity, yield, size distribution, islet morphology score, viability, and function in each islet preparation were analyzed. We found that at digestion stage, T2D pancreases need significantly longer digestion duration and have worse digestion rates and lower gross islet yields. At purification stage, T2D pancreases have poorer purity, purification rate, morphology score, and islet yields after purification. Functional evaluation by GSI assay showed that the human T2D islets have significantly lower glucose stimulated insulin secretion ability. In conclusion, the features of longer digestion duration, lower yields and quality, and impaired insulin secretion in T2D group are consistent with the pathological condition of this disease. Both islet yields and islet function evaluation results did not support human T2D islets as clinical transplantation resources. However, they could serve as good research models for T2D disease studies and promote the advancement of diabetes research.

Keywords: Human islet preparation; Type 2 diabetes mellitus; islet morphology; islet of Langerhans; islet purity; islet quality; islet yield.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay
  • Diabetes Mellitus, Type 2*
  • Humans
  • Pancreas
  • Research
  • Tissue Donors

Grants and funding

This work was supported by National Key Research and Development Program of China (2020YFA0803704), National Natural Science Foundation of China (82070805, 82100841, 82100840, 82200890), Tianjin Municipal Science and Technology Bureau (20JCQNJC01720, 21JCQNJC01850), Tianjin Municipal Human Resources and Social Security Bureau (XB202011), Tianjin Municipal Health Commission (ZC20222), Tianjin First Central Hospital (2020CL01, Youth Talent Cultivation Program to R. Liang.).