IDE's: Insulin Degrading Enzymes
Jul 17, 2016 15:06:29 GMT -5
sportsrancho, lakon, and 1 more like this
Post by cm5 on Jul 17, 2016 15:06:29 GMT -5
Re: Insulin Degrading Enzymes (IDE's), IgF, Insulin--
Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer's disease: review and hypothesis
www.sciencedirect.com/science/article/pii/S0197458005000199
www.tandfonline.com/doi/abs/10.1080/07853890.2016.1197416
IDE's www.nature.com/nature/journal/v443/n7113/abs/nature05143.html
Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?
Review Article
Acta Diabetologica
June 2015, Volume 52, Issue 3, pp 433-443
Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer's disease: review and hypothesis
www.sciencedirect.com/science/article/pii/S0197458005000199
Clinical and epidemiological studies have found that type 2 diabetes, and hyperinsulinaemia, increased the risk of developing Alzheimer's disease (AD) in the elderly.
The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-β peptide (Aβ), a short peptide found in excess in the AD brain.
We review the current evidence, which suggests that hyperinsulinaemia may elevate Aβ through insulin's competition with Aβ for IDE.
Genetic studies have also shown that IDE gene variations are associated with the clinical symptoms of AD as well as the risk of type 2 diabetes. The deficiency of IDE can be caused by genetic variation or by the diversion of IDE from the metabolism of Aβ to the metabolism of insulin. It is intriguing to notice that both hyperinsulinaemia and IDE gene variations are related to the risk of AD when the Apolipoprotein E4 (ApoE4) allele, the major risk factor of late-onset AD, is not present. Further studies of the role of IDE in the pathogenesis of AD, which may uncover potential treatment target, are much needed.
The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-β peptide (Aβ), a short peptide found in excess in the AD brain.
We review the current evidence, which suggests that hyperinsulinaemia may elevate Aβ through insulin's competition with Aβ for IDE.
Genetic studies have also shown that IDE gene variations are associated with the clinical symptoms of AD as well as the risk of type 2 diabetes. The deficiency of IDE can be caused by genetic variation or by the diversion of IDE from the metabolism of Aβ to the metabolism of insulin. It is intriguing to notice that both hyperinsulinaemia and IDE gene variations are related to the risk of AD when the Apolipoprotein E4 (ApoE4) allele, the major risk factor of late-onset AD, is not present. Further studies of the role of IDE in the pathogenesis of AD, which may uncover potential treatment target, are much needed.
Insulin-degrading enzyme (IDE) is a major enzyme responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and beta-amyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer’s disease (AD
IDE's www.nature.com/nature/journal/v443/n7113/abs/nature05143.html
Insulin-degrading enzyme (IDE), a Zn2+-metalloprotease, is involved in the clearance of insulin and amyloid-beta. Loss-of-function mutations of IDE in rodents cause glucose intolerance and cerebral accumulation of amyloid-beta, whereas enhanced IDE activity effectively reduces brain amyloid-beta (refs 4–7). Here we report structures of human IDE in complex with four substrates (insulin B chain, amyloid-beta peptide (1–40), amylin and glucagon). The amino- and carboxy-terminal domains of IDE (IDE-N and IDE-C, respectively) form an enclosed cage just large enough to encapsulate insulin.
Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?
Review Article
Acta Diabetologica
June 2015, Volume 52, Issue 3, pp 433-443
Growth hormone/insulin-like growth factor (IGF) axis may play a role in maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1 hybrid receptors.
In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes.
An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term.
In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk.
In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes.
An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term.
In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk.