INTRODUCTION:

The inability of the insulin hormone in the pancreatic gland to lessen the body's blood glucose levels is one of the signs of diabetes mellitus (DM) sufferers¹.The WHO reports which diabetes mellitus has grown to be a worldwide health issuealong with approximately there were 422 million deaths worldwide in 2014 and 1.5 million deaths worldwide with the same instances in 2019².Diabetes mellitus is a deadly long-term disease and has a high mortality rate throughout the world.

According to According to data from the International Diabetes Federation, eight deaths per minute, or more than one in ten persons between the ages of 20 and 70, were caused by diabetes mellitus in 2019. In addition, the prevalence of diabetes increased by 88% from 2006 to 2019. The growing diabetes mellitus epidemic poses a very significant public health risk³. The number of deaths caused by diabetes mellitus worldwide is largely due to rapid economic growth and high social burden⁴.

Diabetes mellitus affects the body's physiological system as a whole and can cause problems in several organs including the kidneys, eyes, and nerves⁵. Therefore, if people already suffer from diabetes mellitus, they must take blood glucose-lowering medication continuously which is needed to increase the sensitivity and performance of the insulin hormone and regulate its secretion⁶.Pancreatic beta cells have a significant impact on the development of diabetes mellitus because of their ability to secrete the hormone insulin, which has an impact on reducing the body's blood glucose levels⁷.The role of the pancreas gland is the secretion of insulin hormone, which functions as the main messenger to transport glucose from food through the body's cells, where energy is produced⁷.If insulin resistance occurs, it will cause an increase in glucose levels in the body, thereby triggering type 2 diabetes mellitus, which if left untreated will have an impact on pancreatic beta cell dysfunction⁸.There is evidence to show that loss of pancreatic beta cells can have fatal consequences e I and type II diabetes mellitus are prevalent, where the pancreatic gland cannot function properly to secrete insulin to reduce blood glucose levels in a sustainable manner⁷.The primary feature in the initial phases of diabetes mellitus is the appearance of pancreatic beta cell malfunction, whereas the primary feature in the later stages is the total loss of pancreatic beta cell mass at later stages which worsens diabetes mellitus⁹.

Apart from that, continuous metabolic stress like endoplasmic reticulum stress and oxidative stress, and inflammatory replies can also trigger damage to pancreatic beta cells¹⁰.The real impact of increasing reactive oxygen species (ROS) is that it triggers pathogenesis and beta cell dysfunction in diabetes mellitus sufferers¹⁰. The hormone insulin, which is released by beta cells in the pancreas, lowers blood glucose levels and is essential for preserving glucose homeostasis¹¹.(Ahrén, 2022) reported that there is a connection between the amount of glucose given and the pancreatic beta cells' sensitivity to insulin, both in vivo and in vitro, that can help improve how research experiments are designed to observe the results of the secretion of the insulin hormone¹². Pancreatic beta cell failure caused by a decrease in mass and functional damage to makeresearchers are reviewing the development of diabetes mellitus because of pancreatic beta cells¹³.

Physical activity is highly recommended for people with diabetes mellitus.Exercise can help prevent degenerative diseases because it can improve human health and reduce the death rate due to degenerative diseases¹⁴.Exercise has been widely studied at the cellular and systems level in humans, but not many studies have investigated its direct impact on beta cell function and survival.Previous research results show that the physical fitness level of people with diabetes mellitus is different from normal people without diabetes mellitus as measured by the results of the VO2 Max test, as a response to sports training¹⁵.In addition, exercise has not been studied much at the cell biology level.Various components released into the circulation during physical activity also contribute to changes in pancreatic beta cells during exercise¹⁶.But whether exercise may improve the bulk and function of pancreatic beta cells in people with type 2 diabetes mellitus is still largely unknown. Therefore, to increase understanding of the effects of physical activity as a non-pharmacological therapy for diabetes mellitus, a There has to be a comprehensive study of how exercise affects diabetes mellitus¹⁷.

Because there is relevance of pancreatic beta cells to the onset of diabetes mellitus and the benefits obtained from exercise, especially pancreatic beta cell function and survival. This study aims to analyze the effects of exercise on the mass and function of pancreatic beta cells.

MATERIALS AND METHODS:

Studi Design:

This type of systematic review research uses searches from journal databases such as Science Direct, Pubmed, and Web of Science.

Eligibility criteria:

The inclusion criteria for this study are studies that discuss the hormone insulin, pancreatic beta cells, diabetes mellitus, and physical activity published in the last five years (2018-2023). The exclusion criteria for this research are publications published in non-reputable journals or not indexed by Scopus and Web of Science.

Procedure:

Article titles, abstracts, and complete texts were vetted, confirmed, and entered into Mendeley software. In the first stage, 447 papers in all were found using the databases Scopus, Web of Science Pubmed, and Embase. Next, in the second stage, 278 articles were screened based on the suitability of the title and abstract. In the third stage, 63 articles were verified for further processing. At this stage we filter based on the suitability of the full article. Next, in the final stage, 10 articles that met the inclusion criteria were selected and analyzed for this systematic review. For this systematic review, ten publications in total that satisfied the inclusion criteria were chosen and examined. This study adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) evaluation for standard operating procedures.

Figure 1. PRISMA flowchart of the article selection process

RESULTS:

Table 1. Results of a review of the effects of exercise improve beta cell mass and function

Author	SampleCharacteristics	Study Design	Intervention	Results
(Nurdin et al., 2019)¹⁸	30 Wistar rats weighing 200-300 grams were divided into 3 groups, namely K1 control without treatment, K2 given 35 mg streptozotocin/Kg body weight, K3 given 35 mg streptozotocin/Kg body weight and physical exercise.	Experimental	Moderate intensity swimming in the K3 group 4 times a week for 4 weeks.	The K3 group had a higher number of pancreatic beta cells than K2, and K3 had a larger islet of Langerhans width than the K2 group.
(Bronczek et al., 2021)¹⁹	Two groups of mice were created: the treatment group and the control group.	Experimental	Training for 10 weeks with an intensity of each exercise of 75%	The therapy group had an improvement in pancreatic beta cell activity.
(Legaard et al., 2023)¹⁷	82 Adults were divided into 4 groups	Experimental	Training 3 times a week and 6 times a week for 16 weeks of treatment	There was a positive increase in pancreatic beta cell function in the treatment group
(Özdamar et al., 2022)²⁰	Two groups consisting of fourteen adult women were created: the treatment group and the control group.	Experimental	Nordic Walking training for 12 weeks	There was a positive increase in pancreatic beta cell function in the treatment group
(Coomans De Brachène et al., 2023)²¹	46 Healthy participants 26 women and 20 men took part in this study	Experimental	Training included high-intensity interval training, sprint interval training, continuous high-intensity training, and high-intensity functional training. The intervention was performed three times a week for eight weeks without therapy in a control group.	There was a positive increase in pancreatic beta cell function in the treatment group
(Jensen et al., 2023)²²	Adults aged 18 – 65 years contributed to this research	Experimental	Participants were divided into 4 groups, namely the first exercise + placebo, liraglutide + usual activities, a combination of exercise + liraglutide, placebo + usual activities. Participants performed moderate to vigorous intensity physical exercise 4x a week for 52 weeks	There was a positive increase in pancreatic beta cell function in the liraglitide + exercise combination treatment group
(Villaça et al., 2021)²³	A total of thirty-two mice were split into two groups: the treatment group and the control group.	Experimental	Training consisted of treadmill at 70% of maximum speed for 60 minutes per day, 5 days per week for 8 weeks	There was an increase in the mass and function of pancreatic beta cells in the treatment group
(Yuan et al., 2020)²⁴	248 adults contributed to this research divided into 3 groups, namely 83 samples from the aerobic training group, 82 samples from the resistance training group, 83 samples from the control group	Experimental	Training consists of aerobic training at 60% - 70% maximum heart rate and resistance training 3x a week for 6 months	There was an increase in the mass and function of pancreatic beta cells in the treatment group
(Leite et al., 2021)²⁵	Rats were divided into 4 treatment groups, namely sedentary control group, sedentary control treated with melatonin, trained sedentary control, trained sedentary control given melatonin	Experimental	Physical exercise is carried out 5 times per week for 12 weeks	There was an increase in the mass and function of pancreatic beta cells in the treatment group
(Zhang et al., 2023)²⁶	10 adults consisting of 7 men and 3 women participated in this study	Experimental	Moderate intensity resistance training with 45 – 60 minutes per training session for 4 sessions per week and carried out during 10 weeks of intervention	There was an increase in the mass and function of beta cells after being given physical training treatment

DISCUSSIONS:

By using various laboratory analysis techniques, pancreas samples from diabetes mellitus patients showed a reduction in the quantity of beta cells⁷.Few research have looked at the growth of pancreatic beta cell mass, particularly in individuals with pre-diabetes mellitus who are younger in age²⁵.Regular exercise is known to contribute to improving metabolic illnesses including obesity and may raise the sensitivity of the insulin hormone ²⁶.Therefore, research results show that regular exercise is strongly suggested since it helps enhance glycemic management to prevent diabetes mellitus²⁷.This might lessen the long-term negative consequences of consuming too much food, and may also prevent the buildup of fat in the liver together with other metabolic illnesses²⁸.Furthermore, the data currently available indicates that aerobic exercise can enhance glucose metabolism and insulin sensitivity via a variety of molecular pathways, including increased beta cell function, decreased adipokines, normalization of redox status, and upregulation of insulin transporters on cell membranes²⁹.

Study results show that physical activity can prevent insulin resistance³⁰. Research indicates that those with diabetes mellitus are at risk of reduced muscle mass and physical performance decreases two to three times³¹. Exercise can also help the body experience the autophagy phase, where damaged cells are eaten by other cells³². This has been shown for both long-term and short-term exercise.Macrophages are largely responsible for the regulation of muscle stem cells³³. Previous research showed that adults with type 2 diabetes had increased pancreatic beta cell capacity when they exercised²⁶. Higher levels of beta cell dysfunction were also linked to beta cell loss in type 1 diabetes mellitus, according to the same investigation³⁴.

Previous research results show that physical activity improves function of beta cells and reduces fat content in the pancreas³⁵. In the latest research results from Heiskanen et al., 2019, It was noted that following 14 weeks of vigorous exercise it had an effect in reducing lipid accumulation in the pancreatic gland and could enhance the function of the pancreatic beta cells in individuals with type 2 diabetes mellitus and those without the condition³⁵. This is caused by the gluconeogenesis mechanism, namely the process of breaking down muscle fat for energy needs¹⁸. Several other research evidences show that physical exercise can increase pancreatic beta cell mass through various mechanism processes such as proliferation, apoptosis, and beta cell viability²⁵. Other functional capabilities of beta cells, such as insulin secretion, glucose balance, and insulin content can also be improved through exercise¹⁶. In relation to exercise and pancreatic beta cell health, there are many factors to consider, including duration, intensity, frequency, volume, and dose of exercise¹⁶.

The following is a mechanism by which exercise training potentially enhance the mass and functionality of beta cells in the pancreas.By doing physical activity, growth hormone (GH), insulin-like growth factor (IGF-1), glucagon-like peptide 1 (GLP-1), interleukin 6 (IL-6), and interleukin 1 (IL-1) are among the hormones that are more prevalent in the blood³⁶. All of this is thought to have a positive impact on increasing pancreatic beta cell mass²⁹. This rise in beta cell mass is triggered by GH which is able to protect beta cell lines against apoptotic cells which result in cell death³⁷.Research results show that there is an increase in beta cell mass during exercise which is triggered by signals from IGF-1³⁸.

It is true that circulating IGF-1 levels can increase along with pancreatic beta cell proliferation³⁹. Decreased GH levels are associated with decreased mass and proliferation of pancreatic beta cells³⁷.Meanwhile, a decrease in the hormone insulin is also associated with a reduction in the mass and functionality of beta cells in the pancreas³⁹(Castell et al., 2022). The rise in mass of beta cells during pathological and physiological stress depends on beta cell proliferation⁴⁰. The somatotropic axis, which includes GH, insulin-like growth factors (IGF-I and IGF-II), carrier proteins, and related receptors, is a crucial metabolic regulator⁴¹. Diabetes mellitus is brought on by chronic hyperglycemia, lipotoxicity, oxidative stress, and inflammation. These factors can lead to beta cell malfunction, differentiation, and death⁴². The hypothalamic neuropeptides somatostatin and GH-releasing hormone (GHRH), which both promote and inhibit GH secretion, are primarily in charge of GH secretion in the anterior pituitary⁴³. GH is the primary secretory agent of IGF-I, which regulates GH secretion, and influences many body systems⁴⁴. There is evidence that acute aerobic exercise can increase GH. Intensity, volume, and effect of frequency and length of exercise all contribute to these changes ⁴⁵.

So physical exercise is very beneficial in increasing beta cell mass and function in the pancreas through increasing GH and IGF-1.Next, for more details regarding the mechanism of physical exercise increasing pancreatic beta cell mass and function, let's look at Figure 2.

Figure 2. The Mechanism of Physical Exercise Increases the Mass and Function of Pancreatic Beta Cells

CONCLUSSIONS:

Exercise is really beneficial for increasing the sensitivity of the insulin hormone.This increase is triggered by an expansion in the size and capacity of pancreatic beta cells.Growth hormone triggers an increase in IGF-1 which causes pancreatic beta cells to experience proliferation.Physical exercise is highly recommended to maintain body health, especially increasing the size and purpose of the pancreatic beta cells, which are involved in preserving the equilibrium of energy.

ACKNOWLEDGMENTS:

The author would like to thank BPPT and LPDP as funders/sponsors.

CONFLICTS OF INTEREST:

The authors declare no conflict of interest.

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Received on 13.02.2024 Revised on 11.05.2024

Accepted on 14.07.2024 Published on 24.12.2024

Available online from December 27, 2024

Research J. Pharmacy and Technology. 2024;17(12):6112-6117.

DOI: 10.52711/0974-360X.2024.00927