The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and cosecreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, ...The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and cosecreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20 G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which ...Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which is known,requiring permanent care.This poses a major socio-economic burden on healthcare systems as AD patients’relatives and healthcare workers are forced to cope with rising numbers of affected people.Despite recent advances,AD pathological mechanisms are not fully understood.Nevertheless,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in AD patients’brains,plays a key role.Type 2 diabetes,the most common form of diabetes,affects hundreds of million people globally.Islet amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreatic β-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and satiation.Similarly to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and death.It is now clear that IAPP can also have a pathological role in AD,decreasing cognitive function.IAPP harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated dementia.IAPP can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of AD.Thus,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”AD hypothesis.Such approach helps to set a conceptual framework for future IAPP-based drugs against AD.展开更多
The relation between bone remodelling and energy expenditure is an intriguing,and yet unexplained,challenge of the past ten years. In fact,it was only in the last few years that the skeleton was found to function,not ...The relation between bone remodelling and energy expenditure is an intriguing,and yet unexplained,challenge of the past ten years. In fact,it was only in the last few years that the skeleton was found to function,not only in its obvious roles of body support and protection,but also as an important part of the endocrine system. In particular,bone produces different hormones,like osteocalcin(OC),which influences energy expenditure in humans. The undercarboxylated form of OC has a reduced affinity for hydroxyapatite; hence it enters the systemic circulation more easily and exerts its metabolic functions for the proliferation of pancreatic β-cells,insulin secretion,sensitivity,and glucose tolerance. Leptin,a hormone synthesized by adipocytes,also has an effect on both bone remodelling and energy expenditure; in fact it inhibits appetite through hypothalamic influence and,in bone,stimulates osteoblastic differentiation and inhibits apoptosis. Leptin and serotonin exert opposite influences on bone mass accrual,but several features suggest that they might operate in the same pathway through a sympathetic tone. Serotonin,in fact,acts via two opposite pathways in controlling bone remodelling: central and peripheral. Serotonin product by the gastrointestinal tract(95%) augments bone formation by osteoblast,whereas brain-derived serotonin influences low bone mineral density and its decrease leads to an increase in boneresorption parameters. Finally,amylin(AMY) acts as a hormone that alters physiological responses related to feeding,and plays a role as a growth factor in bone. In vitro AMY stimulates the proliferation of osteoblasts,and osteoclast differentiation. Here we summarize the evidence that links energy expenditure and bone remodelling,with particular regard to humans.展开更多
文摘The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and cosecreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20 G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes.
基金supported by iNOVA4Health-UID/Multi/04462/2019,a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência,through national funds and co-funded by FEDER under the PT2020 Partnership Agreement,Funding from INTERFACE Programme,through the Innovation,Technology and Circular Economy Fund(FITEC),FCT via PTDC/BIA-MOL/31104/2017 and UID/Multi/04462/2019-SubProj iNOVA4Health C44(to RM),PD/BD/135504/2018(to AFR)Sociedade Portuguesa de Diabetologia for the Nuno Castelo-Branco Prize-2016(to RM),and ICM acknowledges FCT-MCTES Program“Concurso de Estímulo ao Emprego Científico”(CEECIND/01670/2017).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder that affects millions worldwide.Due to population ageing,the incidence of AD is increasing.AD patients develop cognitive decline and dementia,features for which is known,requiring permanent care.This poses a major socio-economic burden on healthcare systems as AD patients’relatives and healthcare workers are forced to cope with rising numbers of affected people.Despite recent advances,AD pathological mechanisms are not fully understood.Nevertheless,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in AD patients’brains,plays a key role.Type 2 diabetes,the most common form of diabetes,affects hundreds of million people globally.Islet amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreatic β-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and satiation.Similarly to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and death.It is now clear that IAPP can also have a pathological role in AD,decreasing cognitive function.IAPP harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated dementia.IAPP can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of AD.Thus,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”AD hypothesis.Such approach helps to set a conceptual framework for future IAPP-based drugs against AD.
文摘The relation between bone remodelling and energy expenditure is an intriguing,and yet unexplained,challenge of the past ten years. In fact,it was only in the last few years that the skeleton was found to function,not only in its obvious roles of body support and protection,but also as an important part of the endocrine system. In particular,bone produces different hormones,like osteocalcin(OC),which influences energy expenditure in humans. The undercarboxylated form of OC has a reduced affinity for hydroxyapatite; hence it enters the systemic circulation more easily and exerts its metabolic functions for the proliferation of pancreatic β-cells,insulin secretion,sensitivity,and glucose tolerance. Leptin,a hormone synthesized by adipocytes,also has an effect on both bone remodelling and energy expenditure; in fact it inhibits appetite through hypothalamic influence and,in bone,stimulates osteoblastic differentiation and inhibits apoptosis. Leptin and serotonin exert opposite influences on bone mass accrual,but several features suggest that they might operate in the same pathway through a sympathetic tone. Serotonin,in fact,acts via two opposite pathways in controlling bone remodelling: central and peripheral. Serotonin product by the gastrointestinal tract(95%) augments bone formation by osteoblast,whereas brain-derived serotonin influences low bone mineral density and its decrease leads to an increase in boneresorption parameters. Finally,amylin(AMY) acts as a hormone that alters physiological responses related to feeding,and plays a role as a growth factor in bone. In vitro AMY stimulates the proliferation of osteoblasts,and osteoclast differentiation. Here we summarize the evidence that links energy expenditure and bone remodelling,with particular regard to humans.
