INTRODUCTION

Type 1 diabetes, also known as insulin-dependent diabetes, is an autoimmune disease in which blood sugar levels are higher than normal due to deficiency or absence of insulin, resulting from the destruction of pancreatic beta cells (1). Ten percent of all diabetics have Type 1 diabetes, which is increasing in adolescent groups (2). The causes of Type 1 diabetes include genetic factors, autoimmunity, and viral infection (3). Currently, there is no definitive treatment for Type 1 diabetes, and although insulin injections are the only treatmen, they can leade to various complications (3). People with Type 1 diabetes suffer from diabetes complications such as: impaired renal function, reduced vision and blindness, reduced skin sensation and lower torso ulcers, cardiovascular disease, and most importantly, reduced life expectancy (3). This is probably because insulin injections cannot be as effective as normal insulin secretion in the body (40). Due to the limitations of antidiabetic drugs, it is essential to find new compounds that can replace or supplement treatment against the disease (4). Some findings suggest that exercise can be used to treat and prevent a number of diseases (5). In these patients, exercise can also improve insulin function in the body by increasing sensitivity and reducing insulin resistance, thereby reducing the dosage of injected insulin (6). Glypicon 4 (also known as CPD-4), a family of heparin sulfate proteoglycans and a component of extracellular proteins, are bound to the cell surface via a glycophosphatidylinositol and affect insulin signaling through insulin receptor interaction (IR) (7), thereby increasing the signaliging process (7). Special Glycophosphatidylinositol D in insulinoma cells in pancreatic beta cells has led to the hypothesis that this enzyme may be involved in diabetes (8) or be influenced by various diabetic conditions (8). It is also found in abundance in mammalian serum. In addition, special phosphatidylinositol phosphorylase D may play a key role in inflammation and pathogenicity of diabetics (8) Chamomile has a long history as a medicinal plant due to its many health benefits such as anti-inflammatory, anti-cancer, antispasmodic and radical effects (18). On the other hand, few studies examined the effects of exercise programs on serum insulin levels, phosphatidylinositol glycan-specific phospholipase D, glypican-4, especially in Type 1 diabetes. Therefore, this study investigates the effects of 12 weeks of dietary aerobic exercise and hydroatanol extract of chamomile flowers on serum insulin levels, phosphatidylinositol glycan-specific phospholipase, and glypican-4 rat with Type 1 diabetes.

METHODS

In this experimental study, Type 1 diabetes was induced in 24 male Vistar rats by injecting streptozotocin (STZ) in a saline solution. They were randomly divided into four groups (control group, exercise +chamomile , extract ,exercise): a control group and a chamomile extract group (receiving 200 mg of chamomile extract per kg of body weight per day for 12 weeks, five days per week, 60 min per session). Serum levels of glypican-4, fasting blood insulin, phosphatidylinositol, glycan-specific phospholipase D, and glypican-4 in blood were measured by ELISA at the end of the study. The collected data were analyzed using one-way ANOVA, followed by post-hoc tests. A P-value < 0.05 was considered statistically significant, and all the analyses were performed in SPSS software (version 29).

RESULTS

Compared to the control group, serum insulin levels were significantly lower in the exercise group and the extract group; however, the levels of phosphatidylinositol, particularly phosphorylase D, were not significant (P>0.05). Furthermore, changes in glypican-4 were noted.

CONCLUSION

According to the findings of this study, it seems that both fully aerobic exercise, chamomile extract consumption, and their combination, all three reduce the level of fasting insulin factors that affect the progression of diabetes. However, no significant difference was observed among these three interventions. In other words, aerobic exercise alone, chamomile extract consumption alone, and their combined application yielded similar effects. Therefore, none of these methods seem to be superior to the others. The results also suggest that serum levels of phosphatidylinositol-specific phosphorylase D may decrease after endurance training and extract use, possibly due to advances in insulin profile. Endurance training with the extract may not be compatible with glypikon-4 circulation.

Ethical Considerations
Compliance with ethical guidelines
All ethical principles for working with animals were approved in accordance with the Helsinki Declaration and under supervision of the Ethics Committee of University of Bu-Ali Sina with the code Rec.umsha.ac.1r1401.03

Funding
The authors declare that no funding was received for this research.

Authors' Contributions
All Authors contributed to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest
The authors have declared that there are no conflicts of interest.

Acknowledgments
We sincerely thank Dr. Haidarianpour, who provided invaluable guidance and contributed significantly to the design of this study, as well as the patients who patiently supported us throughtout this research process.