Low-Level Insulin Content Within Abundant Non-β Islet Endocrine Cells in Long-standing Type 1 Diabetes.

Abstract:

:Although most patients with type 1 diabetes (T1D) continue to produce small amounts of insulin decades after disease onset, very few β-cells persist within their pancreata. Consequently, the source of persistent insulin secretion within T1D remains unclear. We hypothesized that low-level insulin content within non-β-cells could underlie persistent T1D insulin secretion. We tested for low levels of insulin (insulinlow) within a large cohort of JDRF Network for Pancreatic Organ Donors With Diabetes (nPOD) human pancreata across a wide range of ages and T1D disease durations. Long exposures, high-throughput imaging, and blinded parallel examiners allowed precise quantification of insulinlow cells. Of note, abundant islet endocrine cells with low quantities of insulin were present in most T1D pancreata. Insulinlow islet abundance and composition were not influenced by age, duration of diabetes, or age of onset. Insulinlow islets also contained β-cell markers at variable levels, including Pdx1, Nkx6.1, GLUT1, and PC1/3. Most insulinlow cells contained abundant glucagon and other α-cell markers, suggesting that α-cells drive much of the insulinlow phenotype in T1D. However, pancreatic polypeptide, somatostatin, and ghrelin cells also contributed to the insulinlow cell population. Insulinlow cells represent a potential source of persistent insulin secretion in long-standing T1D and a possible target for regenerative therapies to expand β-cell function in disease.

journal_name

Diabetes

journal_title

Diabetes

authors

Lam CJ,Chatterjee A,Shen E,Cox AR,Kushner JA

doi

10.2337/db18-0305

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

598-608

issue

3

eissn

0012-1797

issn

1939-327X

pii

db18-0305

journal_volume

68

pub_type

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