Abstract
Study background: Type 1 diabetes is an insulin-dependent diabetes mellitus (IDDM) because the body does not produce sufficient insulin for daily need. Persistent high glucose level in the blood circulation can stimulate the advanced glycation end products/receptor for AGEs (AGE/RAGE) pathway leading to diabetic complications. Currently, there is no preventive measure for IDMM with only treatment focusing on delaying the onset of diabetic complications. This study aimed to investigate how the different insulin regimens given affect the glycemic control and glucose metabolism in type 1 diabetes. The effects on the AGE/RAGE axis were determined as well. Methods: Twenty-one male Sprague-Dawley rats were randomly assigned into three groups (Group A: streptozotocin-induced diabetic rats given high-dose insulin [5-7U per day], Group B: streptozotocin-induced diabetic rats given low-dose insulin [0-3U per day], Group C: non-diabetic control). Throughout the eight-week treatment, the body weight, systolic blood pressure and non-fasting blood glucose concentration were monitored. After eight weeks of treatment, fasting blood glucose concentration, glycated haemoglobin (HbA1c), nuclear factor kappa B (NF-κB), AGE level and RAGE expression were measured. Results: High-dose insulin treatment impaired glucose metabolism. On the contrary, diabetic rats receiving lowdose insulin showed reduced glucose level and improved insulin sensitivity towards the end of experiment. HbA1c level was significantly lower in low-dose insulin treated rats while NF-κB level was significantly lower in high-dose insulin treated rats (p ≤ 0.05). There was no significant difference in AGE levels in all the groups (p>0.05) and only the heart tissues from the low-dose insulin treated group showed significant down regulation of the RAGE gene expression (p ≤ 0.05). Conclusion: Low-dose insulin treatment was shown to be a better therapeutic intervention for type 1 diabetes.
Highlights
Diabetes mellitus is a group of metabolic diseases characterized by increased blood glucose levels
HbA1c level was significantly lower in low-dose insulin treated rats while NF-κB level was significantly lower in high-dose insulin treated rats (p ≤ 0.05)
There was no significant difference in Advanced glycation end products (AGEs) levels in all the groups (p>0.05) and only the heart tissues from the low-dose insulin treated group showed significant down regulation of the receptor for advanced glycation end products (RAGE) gene expression (p ≤ 0.05)
Summary
Diabetes mellitus is a group of metabolic diseases characterized by increased blood glucose levels (hyperglycemia). This abnormal elevation of blood glucose occurs due to defects in insulin secretion, insulin action or both [4]. There are different types of diabetes based on the aetiology and clinical stages. Type 1 diabetes is known as insulin-dependent diabetes mellitus (IDDM) because the body does not produce sufficient insulin for daily need and regular insulin injections are required [4]. There is no preventive measure for IDMM with only treatment focusing on delaying the onset of diabetic complications. Insulin therapy is a common treatment for IDMM. Insulin dosage should be individualized, designing an ideal insulin regimen for reference are undoubtedly of utmost interest
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