Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes

Type 1 diabetes (T1D) is related to the autoimmune destruction of β-cells, leading to their almost complete absence in patients with longstanding T1D. However, endogenous insulin secretion persists in such patients as evidenced by the measurement of plasma C-peptide. Recently, a low level of insulin...

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Main Authors: Yuliya Krivova, Alexandra Proshchina, Dmitry Otlyga, Anastasia Kharlamova, Sergey Saveliev
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/1/125
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author Yuliya Krivova
Alexandra Proshchina
Dmitry Otlyga
Anastasia Kharlamova
Sergey Saveliev
author_facet Yuliya Krivova
Alexandra Proshchina
Dmitry Otlyga
Anastasia Kharlamova
Sergey Saveliev
author_sort Yuliya Krivova
collection DOAJ
description Type 1 diabetes (T1D) is related to the autoimmune destruction of β-cells, leading to their almost complete absence in patients with longstanding T1D. However, endogenous insulin secretion persists in such patients as evidenced by the measurement of plasma C-peptide. Recently, a low level of insulin has been found in non-β islet cells of patients with longstanding T1D, indicating that other islet cell types may contribute to persistent insulin secretion. The present study aimed to test the ability of various antibodies to detect insulin in insulin-deficient islets of T1D patients. Pancreatic autopsies from two children with recent-onset T1D, two adults with longstanding T1D, and three control subjects were examined using double immunofluorescent labeling with antibodies to insulin, glucagon and somatostatin. Immunoreactivity to insulin in glucagon+ cells of insulin-deficient islets was revealed using polyclonal antibodies and monoclonal antibodies simultaneously recognizing insulin and proinsulin. Along with this, immunoreactivity to insulin was observed in the majority of glucagon+ cells of insulin-containing islets of control subjects and children with recent-onset T1D. These results suggest that islet α-cells may contain insulin and/or other insulin-like proteins (proinsulin, C-peptide). Future studies are needed to evaluate the role of α-cells in insulin secretion and diabetes pathogenesis.
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spelling doaj-art-a8030fac025e48fa86b7a7c27ef236042025-01-24T13:38:54ZengMDPI AGLife2075-17292025-01-0115112510.3390/life15010125Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 DiabetesYuliya Krivova0Alexandra Proshchina1Dmitry Otlyga2Anastasia Kharlamova3Sergey Saveliev4Laboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Tsurupi Street, 3, 117418 Moscow, RussiaLaboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Tsurupi Street, 3, 117418 Moscow, RussiaLaboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Tsurupi Street, 3, 117418 Moscow, RussiaLaboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Tsurupi Street, 3, 117418 Moscow, RussiaLaboratory of Nervous System Development, Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, Tsurupi Street, 3, 117418 Moscow, RussiaType 1 diabetes (T1D) is related to the autoimmune destruction of β-cells, leading to their almost complete absence in patients with longstanding T1D. However, endogenous insulin secretion persists in such patients as evidenced by the measurement of plasma C-peptide. Recently, a low level of insulin has been found in non-β islet cells of patients with longstanding T1D, indicating that other islet cell types may contribute to persistent insulin secretion. The present study aimed to test the ability of various antibodies to detect insulin in insulin-deficient islets of T1D patients. Pancreatic autopsies from two children with recent-onset T1D, two adults with longstanding T1D, and three control subjects were examined using double immunofluorescent labeling with antibodies to insulin, glucagon and somatostatin. Immunoreactivity to insulin in glucagon+ cells of insulin-deficient islets was revealed using polyclonal antibodies and monoclonal antibodies simultaneously recognizing insulin and proinsulin. Along with this, immunoreactivity to insulin was observed in the majority of glucagon+ cells of insulin-containing islets of control subjects and children with recent-onset T1D. These results suggest that islet α-cells may contain insulin and/or other insulin-like proteins (proinsulin, C-peptide). Future studies are needed to evaluate the role of α-cells in insulin secretion and diabetes pathogenesis.https://www.mdpi.com/2075-1729/15/1/125human pancreastype 1 diabetesinsulinglucagonpolyhormonal cells
spellingShingle Yuliya Krivova
Alexandra Proshchina
Dmitry Otlyga
Anastasia Kharlamova
Sergey Saveliev
Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
Life
human pancreas
type 1 diabetes
insulin
glucagon
polyhormonal cells
title Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
title_full Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
title_fullStr Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
title_full_unstemmed Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
title_short Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes
title_sort detection of insulin in insulin deficient islets of patients with type 1 diabetes
topic human pancreas
type 1 diabetes
insulin
glucagon
polyhormonal cells
url https://www.mdpi.com/2075-1729/15/1/125
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AT dmitryotlyga detectionofinsulinininsulindeficientisletsofpatientswithtype1diabetes
AT anastasiakharlamova detectionofinsulinininsulindeficientisletsofpatientswithtype1diabetes
AT sergeysaveliev detectionofinsulinininsulindeficientisletsofpatientswithtype1diabetes