Abu Saleh Md Moin1, Ahmed Al-Qaissi2,3, Thozhukat Sathyapalan2, Stephen L Atkin4, Alexandra E Butler1. 1. Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar. 2. Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, UK. 3. Leeds Medical School, Leeds, UK. 4. Royal College of Surgeons of Ireland, Busaiteen, Bahrain.
Abstract
AIMS: Hypoglycaemia in diabetes (T2D) may increase the risk of Alzheimer's disease (AD). We hypothesized that hypoglycaemia-induced amyloid-related protein changes would be exacerbated in T2D. MATERIALS AND METHODS: A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycaemia with blood sampling at baseline, hypoglycaemia and post-hypoglycaemia; proteomic analysis of amyloid-related proteins was undertaken. RESULTS: At baseline, amyloid-precursor protein (APP) (P < .01) was elevated and alpha-synuclein (SNCA) (P < .01) reduced in T2D. At hypoglycaemia, amyloid P-component (P < .01) was elevated and SNCA (P < .05) reduced in T2D; APP (P < .01) and noggin (P < .05) were elevated and SNCA (P < .01) reduced in controls. In the post-hypoglycaemia follow-up period, APP and microtubule-associated protein tau normalized in controls but showed a below-baseline decrease in T2D; noggin normalized in both; SNCA normalized in T2D, with a below-baseline decrease in controls. CONCLUSION: The AD-associated protein pattern found in T2D, with basal elevated APP and reduced SNCA, was exaggerated by hypoglycaemia with increased APP and decreased SNCA. Additional AD-associated protein levels that changed in response to hypoglycaemia, particularly in T2D, included amyloid P-component, microtubule-associated protein tau, apolipoproteins A1 and E3, pappalysin and noggin. These results are in accordance with the reported detrimental effects of hypoglycaemia.
AIMS: Hypoglycaemia in diabetes (T2D) may increase the risk of Alzheimer's disease (AD). We hypothesized that hypoglycaemia-induced amyloid-related protein changes would be exacerbated in T2D. MATERIALS AND METHODS: A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycaemia with blood sampling at baseline, hypoglycaemia and post-hypoglycaemia; proteomic analysis of amyloid-related proteins was undertaken. RESULTS: At baseline, amyloid-precursor protein (APP) (P < .01) was elevated and alpha-synuclein (SNCA) (P < .01) reduced in T2D. At hypoglycaemia, amyloid P-component (P < .01) was elevated and SNCA (P < .05) reduced in T2D; APP (P < .01) and noggin (P < .05) were elevated and SNCA (P < .01) reduced in controls. In the post-hypoglycaemia follow-up period, APP and microtubule-associated protein tau normalized in controls but showed a below-baseline decrease in T2D; noggin normalized in both; SNCA normalized in T2D, with a below-baseline decrease in controls. CONCLUSION: The AD-associated protein pattern found in T2D, with basal elevated APP and reduced SNCA, was exaggerated by hypoglycaemia with increased APP and decreased SNCA. Additional AD-associated protein levels that changed in response to hypoglycaemia, particularly in T2D, included amyloid P-component, microtubule-associated protein tau, apolipoproteins A1 and E3, pappalysin and noggin. These results are in accordance with the reported detrimental effects of hypoglycaemia.
Authors: Stephen L Atkin; Alexandra E Butler; Abu Saleh Md Moin; Ahmed Al-Qaissi; Thozhukat Sathyapalan Journal: J Transl Med Date: 2021-03-31 Impact factor: 5.531
Authors: Abu Saleh Md Moin; Hassan Kahal; Ahmed Al-Qaissi; Nitya Kumar; Thozhukat Sathyapalan; Stephen L Atkin; Alexandra E Butler Journal: BMJ Open Diabetes Res Care Date: 2021-04
Authors: Abu Saleh Md Moin; Manjula Nandakumar; Hassan Kahal; Thozhukat Sathyapalan; Stephen L Atkin; Alexandra E Butler Journal: Cells Date: 2021-11-10 Impact factor: 6.600
Authors: Manjunath Ramanjaneya; Ruth Priyanka; Milin Bensila; Jayakumar Jerobin; Krunal Pawar; Thozhukat Sathyapalan; Abdul Badi Abou-Samra; Najeeb M Halabi; Abu Saleh Md Moin; Stephen L Atkin; Alexandra E Butler Journal: Front Endocrinol (Lausanne) Date: 2022-08-09 Impact factor: 6.055
Authors: Abu Saleh Md Moin; Thozhukat Sathyapalan; Stephen L Atkin; Alexandra E Butler Journal: Cardiovasc Diabetol Date: 2022-10-06 Impact factor: 8.949
Authors: Abu Saleh Md Moin; Ahmed Al-Qaissi; Thozhukat Sathyapalan; Stephen L Atkin; Alexandra E Butler Journal: Front Endocrinol (Lausanne) Date: 2021-06-23 Impact factor: 5.555