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Inhaled insulin for controlling blood glucose in patients with diabetes.

Silverman BL, Barnes CJ, Campaigne BN, Muchmore DB - Vasc Health Risk Manag (2007)

Bottom Line: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates.Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease.The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.

View Article: PubMed Central - PubMed

Affiliation: Alkermes, Inc, Cambridge, MA, USA.

ABSTRACT
Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.

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Related in: MedlinePlus

Summary of diabetes causes and progression. Diabetes represents a collection of disease processes involving progressive systemic loss of tissue sensitivity to insulin signaling and/or the loss of pancreatic β-cell number or function. Changes at the level of intracellular signaling include decreased expression of glucose transport proteins (GLUT4), decreased production of endothelial vasodilators (nitric oxide), increased intracellular oxidative stress (O2-), and release into the systemic circulation of pro-inflammatory (C-reactive protein, IL-6, TNFa) and coagulation (PAI-1, ICAM-1) mediators. These changes are both caused by and lead to decreased glucose absorption in several organs, increased levels of both circulating glucose (hyperglycemia) and non-esterified fatty acids (dyslipidemia), passive glucose diffusion into cells with unregulated glucose uptake, changes in vascular endothelial tone, and formation of atherosclerotic plaques. Glycosylation of intracellular and systemically circulating proteins, increased luminal fatty acid deposition, altered cellular metabolism, and increased clotting contribute to an increased risk for the microvascular and macrovascular risks associated with uncontrolled diabetes.
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fig1: Summary of diabetes causes and progression. Diabetes represents a collection of disease processes involving progressive systemic loss of tissue sensitivity to insulin signaling and/or the loss of pancreatic β-cell number or function. Changes at the level of intracellular signaling include decreased expression of glucose transport proteins (GLUT4), decreased production of endothelial vasodilators (nitric oxide), increased intracellular oxidative stress (O2-), and release into the systemic circulation of pro-inflammatory (C-reactive protein, IL-6, TNFa) and coagulation (PAI-1, ICAM-1) mediators. These changes are both caused by and lead to decreased glucose absorption in several organs, increased levels of both circulating glucose (hyperglycemia) and non-esterified fatty acids (dyslipidemia), passive glucose diffusion into cells with unregulated glucose uptake, changes in vascular endothelial tone, and formation of atherosclerotic plaques. Glycosylation of intracellular and systemically circulating proteins, increased luminal fatty acid deposition, altered cellular metabolism, and increased clotting contribute to an increased risk for the microvascular and macrovascular risks associated with uncontrolled diabetes.

Mentions: Diabetes can arise from a number of initiating conditions that collectively lead to common downstream outcomes (Figure 1). At the cellular level, a variety of cell types develop altered sensitivity to insulin through little known mechanisms (Saltiel and Kahn 2001; Brownlee 2005; Yamagishi and Imaizumi 2005). Specifically, insulin docking with the insulin receptor on the target cell surface normally activates multiple cascades of intracellular signaling. In insulin resistance, one key pathway that includes the signaling kinases phosphatidylinositol-3-kinase and AKT fails to activate, disrupting normal intracellular insulin responsiveness and preventing key proteins involved in glucose uptake from being upregulated by insulin. As a result, cellular uptake of glucose is attenuated, circulating BG remains high, and tissues such as the endothelial lining of blood vessels passively accumulate glucose.


Inhaled insulin for controlling blood glucose in patients with diabetes.

Silverman BL, Barnes CJ, Campaigne BN, Muchmore DB - Vasc Health Risk Manag (2007)

Summary of diabetes causes and progression. Diabetes represents a collection of disease processes involving progressive systemic loss of tissue sensitivity to insulin signaling and/or the loss of pancreatic β-cell number or function. Changes at the level of intracellular signaling include decreased expression of glucose transport proteins (GLUT4), decreased production of endothelial vasodilators (nitric oxide), increased intracellular oxidative stress (O2-), and release into the systemic circulation of pro-inflammatory (C-reactive protein, IL-6, TNFa) and coagulation (PAI-1, ICAM-1) mediators. These changes are both caused by and lead to decreased glucose absorption in several organs, increased levels of both circulating glucose (hyperglycemia) and non-esterified fatty acids (dyslipidemia), passive glucose diffusion into cells with unregulated glucose uptake, changes in vascular endothelial tone, and formation of atherosclerotic plaques. Glycosylation of intracellular and systemically circulating proteins, increased luminal fatty acid deposition, altered cellular metabolism, and increased clotting contribute to an increased risk for the microvascular and macrovascular risks associated with uncontrolled diabetes.
© Copyright Policy
Related In: Results  -  Collection

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fig1: Summary of diabetes causes and progression. Diabetes represents a collection of disease processes involving progressive systemic loss of tissue sensitivity to insulin signaling and/or the loss of pancreatic β-cell number or function. Changes at the level of intracellular signaling include decreased expression of glucose transport proteins (GLUT4), decreased production of endothelial vasodilators (nitric oxide), increased intracellular oxidative stress (O2-), and release into the systemic circulation of pro-inflammatory (C-reactive protein, IL-6, TNFa) and coagulation (PAI-1, ICAM-1) mediators. These changes are both caused by and lead to decreased glucose absorption in several organs, increased levels of both circulating glucose (hyperglycemia) and non-esterified fatty acids (dyslipidemia), passive glucose diffusion into cells with unregulated glucose uptake, changes in vascular endothelial tone, and formation of atherosclerotic plaques. Glycosylation of intracellular and systemically circulating proteins, increased luminal fatty acid deposition, altered cellular metabolism, and increased clotting contribute to an increased risk for the microvascular and macrovascular risks associated with uncontrolled diabetes.
Mentions: Diabetes can arise from a number of initiating conditions that collectively lead to common downstream outcomes (Figure 1). At the cellular level, a variety of cell types develop altered sensitivity to insulin through little known mechanisms (Saltiel and Kahn 2001; Brownlee 2005; Yamagishi and Imaizumi 2005). Specifically, insulin docking with the insulin receptor on the target cell surface normally activates multiple cascades of intracellular signaling. In insulin resistance, one key pathway that includes the signaling kinases phosphatidylinositol-3-kinase and AKT fails to activate, disrupting normal intracellular insulin responsiveness and preventing key proteins involved in glucose uptake from being upregulated by insulin. As a result, cellular uptake of glucose is attenuated, circulating BG remains high, and tissues such as the endothelial lining of blood vessels passively accumulate glucose.

Bottom Line: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates.Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease.The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.

View Article: PubMed Central - PubMed

Affiliation: Alkermes, Inc, Cambridge, MA, USA.

ABSTRACT
Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.

Show MeSH
Related in: MedlinePlus