Reversible changes in pancreatic islet structure and function produced by elevated blood glucose
Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cel...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature publishing
2014
|
| _version_ | 1826272907051925504 |
|---|---|
| author | Brereton, M Iberl, M Shimomura, K Zhang, Q Adriaenssens, A Proks, P Spiliotis, I Dace, W Mattis, K Ramracheya, R Gribble, F Reimann, F Clark, A Rorsman, P Ashcroft, F |
| author_facet | Brereton, M Iberl, M Shimomura, K Zhang, Q Adriaenssens, A Proks, P Spiliotis, I Dace, W Mattis, K Ramracheya, R Gribble, F Reimann, F Clark, A Rorsman, P Ashcroft, F |
| author_sort | Brereton, M |
| collection | OXFORD |
| description | Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than KATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized. |
| first_indexed | 2024-03-06T22:19:58Z |
| format | Journal article |
| id | oxford-uuid:54b07831-5128-406b-bbe7-5aa7af26c057 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:19:58Z |
| publishDate | 2014 |
| publisher | Nature publishing |
| record_format | dspace |
| spelling | oxford-uuid:54b07831-5128-406b-bbe7-5aa7af26c0572022-03-26T16:39:30ZReversible changes in pancreatic islet structure and function produced by elevated blood glucoseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:54b07831-5128-406b-bbe7-5aa7af26c057EnglishSymplectic Elements at OxfordNature publishing2014Brereton, MIberl, MShimomura, KZhang, QAdriaenssens, AProks, PSpiliotis, IDace, WMattis, KRamracheya, RGribble, FReimann, FClark, ARorsman, PAshcroft, FDiabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than KATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized. |
| spellingShingle | Brereton, M Iberl, M Shimomura, K Zhang, Q Adriaenssens, A Proks, P Spiliotis, I Dace, W Mattis, K Ramracheya, R Gribble, F Reimann, F Clark, A Rorsman, P Ashcroft, F Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title | Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title_full | Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title_fullStr | Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title_full_unstemmed | Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title_short | Reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| title_sort | reversible changes in pancreatic islet structure and function produced by elevated blood glucose |
| work_keys_str_mv | AT breretonm reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT iberlm reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT shimomurak reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT zhangq reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT adriaenssensa reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT proksp reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT spiliotisi reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT dacew reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT mattisk reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT ramracheyar reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT gribblef reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT reimannf reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT clarka reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT rorsmanp reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose AT ashcroftf reversiblechangesinpancreaticisletstructureandfunctionproducedbyelevatedbloodglucose |