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