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Ca2+ Oscillations, Waves, and Networks in Islets from Human Donors With and Without Type 2 Diabetes

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posted on 2022-09-09, 21:09 authored by Marko Gosak, Richard Yan-Do, Haopeng Lin, Patrick E. MacDonald, Andraz Stozer

Pancreatic islets are highly interconnected structures that produce pulses of insulin and other hormones, maintaining normal homeostasis of glucose and other nutrients. Normal stimulus-secretion and intercellular coupling are essential to regulated secretory responses and these hallmarks are known to be altered in diabetes. In the present study, we used calcium imaging of isolated human islets to assess their collective behavior. The activity occurred in the form of calcium oscillations, was synchronized across different regions of islets through calcium waves, and was glucose-dependent: higher glucose enhanced the activity, elicited a greater proportion of global calcium waves, and led to denser and less fragmented functional networks. Hub regions were identified in stimulatory conditions and they were characterized by long active times. Moreover, calcium waves were found to be initiated in different subregions and the roles of initiators and hubs did not overlap. In type 2 diabetes, glucose-dependence was retained, but a reduced activity, locally restricted waves, and more segregated networks were detected compared with control islets. Interestingly, hub regions seemed to suffer the most by losing a disproportionately large fraction of connections. These changes affected islets from donors with diabetes in a heterogeneous manner.

Funding

H.L. was supported by a Sino-Canadian Studentship from Shantou University. Research was funded in part by a Human Islet Research Network grant from the National Institutes of Health (U01DK120447). P.E.M. holds the Canada Research Chair in Islet Biology. The authors also acknowledge support of the Slovenian Research Agency (research core funding nos. P3-0396 and I0-0029, as well as research projects nos. J1-2457, N3-0133, J3-9289, J3-3077).

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