Biomedical Engineering Reference
In-Depth Information
Heart
Improve cardiac health
blood pressure, TG, LDL cholesterol
HDL cholesterol
myocardium and vascular function
?
Hypothalamus
Suppressed
appetite
Satiety
Cardiac failure
Obesity
Muscle and adipose tissue
Improved glucose uptake
Intestine
Gastric
emptying
Insulin sensitivity
Insulin
resistance
Pancreas
Liver
Improved energy metabolism
Glucose homeostasis
Insulin secretion
Glucagon secretion
Glycogen synthesis
Glucose production
Improved β -cell health
Insulin biosynthesis
↑β -cell neogenesis
↓β -cell apoptosis
Insulin sensitivity
Less fat accumulation
Lipolysis
Lipogenesis
Feet
Hyperglycemia,
Diabetic
foot
ulcer
Insulin
resistance,
hyperglycemia,
fatty liver diseases
β
-cell dysfunction
Figure 5.3 Benefits and potential benefits of DPP-4 inhibitors.
DPP-4 is upregulated in patients with non-alcoholic fatty liver disease, and
studies in animal models show that ablation of DPP-4 leads to reduced liver
steatosis. 83,91,92 The underlying mechanisms are thought to be due to upregu-
lation of intrahepatic genes involved in fat oxidation such as peroxisome
proliferator activated receptor a (PPARa) and acyl-CoA oxidase (AOX) and
downregulation of lipogenic genes such as sterol regulatory element binding
protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and stearoyl-CoA
desaturase-1 (SCD-1) in the absence of DPP-4. 83,93 Moreover DPP-4 inhibitor
treatment lessens insulin resistance, which is a major determinant of hepatic
steatosis. 91 These findings suggest that DPP-4 inhibitors could be a potential
treatment for non-alcoholic fatty liver disease, which is a common complication
in type 2 diabetes. 91
Type 2 diabetes is associated with a risk of adverse cardiovascular events.
DPP-4 inhibitors decrease cardiac risk factors, blood pressure, triglycerides,
and low-density lipoprotein cholesterol and increase high-density lipoprotein
cholesterol in clinical trials. 81,94 A study examining saxagliptin treatment of
patients with type 2 diabetes speculated on a reduction in cardiovascular
events. 95 Also, DPP-4 inhibitor treatment improves cardiac functions in animal
models of myocardial infarction. 96,97 Several studies have demonstrated that
GLP-1 has direct effects on myocardium and vasculature. 81 Also, the DPP-4
substrates, B-type natriuretic peptide (BNP), and the chemokine SDF-1a have
important roles in cardiac functions. Hence, DPP-4 inhibitor treatment may
 
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