Evidence based study of Hypoglycemic Potential of Bitter Melon Peptide

Diabetes mellitus (DM) was considered as one of the five leading causes of death in the world. It was a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, and attributed to defective insulin secretion, resistance to insulin action, or a combination of both. On the basis of the pathogenic process that lead to hyperglycemia, diabetes was classified into type 1 diabetes (insulin-dependent) and type 2 diabetes (non-insulin-dependent) [1,2]. Ordinarily, the people below 18 age suffered from the type 1 diabetes, whereas type 2 diabetes mainly occurred in adult and old age group. According to the World Health Organization, approximately 10% of all diabetes cases were type 1, and the remaining 90% cases of diabetes worldwide were of type 2, the number of people with DM worldwide had soared from 128 million in 1980 to 422 million in 2014. DM was one of the major threats to human life in many countries. Health-care professionals usually recommend controlling patients’ blood sugar levels through a combination of drugs, diet controls, and regular physical exercise [3-5]. Still, no drug was available which had the ability to completely cure type 2 diabetes. Generally, to treat type 2 diabetes, oral hypoglycemic agents were used [6].


Diabetes Mellitus
Diabetes mellitus (DM) was considered as one of the five leading causes of death in the world. It was a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, and attributed to defective insulin secretion, resistance to insulin action, or a combination of both. On the basis of the pathogenic process that lead to hyperglycemia, diabetes was classified into type 1 diabetes (insulin-dependent) and type 2 diabetes (non-insulin-dependent) [1,2]. Ordinarily, the people below 18 age suffered from the type 1 diabetes, whereas type 2 diabetes mainly occurred in adult and old age group. According to the World Health Organization, approximately 10% of all diabetes cases were type 1, and the remaining 90% cases of diabetes worldwide were of type 2, the number of people with DM worldwide had soared from 128 million in 1980 to 422 million in 2014. DM was one of the major threats to human life in many countries. Health-care professionals usually recommend controlling patients' blood sugar levels through a combination of drugs, diet controls, and regular physical exercise [3][4][5]. Still, no drug was available which had the ability to completely cure type 2 diabetes. Generally, to treat type 2 diabetes, oral hypoglycemic agents were used [6].

Peptides from Bitter Melon
Bitter melon was a common vegetable that displays antidiabetic potential. Many reports indicated that peptide extracts from MC showed various anti-hyperglycemic activities ( Table 1).
The anti-diabetic mechanisms from bitter melon peptide such as α-glucosidase inhibitors, α-amylase inhibitors and insulin mimetics activities were shown in Figure 1.

Abstract
Momordica charantia (M. charantia), commonly referred to as bitter melon was received much attention for its anti-diabetic properties in recent years. The aim of this review was to discuss the bioactive peptides in bitter melon through their in vitro, in vivo and clinical studies for diabetes. Research showed that bitter melon peptides acted as the α-amylase or α-glycosidase inhibitor delayed the absorption of glucose from carbohydrates. Another noteworthy mechanism was the glucose intake regulation by insulin-like activities to enhanced insulin receptor kinase activity which activated IR signaling transduction pathway, resulted the translocation of glucose transporter 4, and uptake of glucose to cells. The remarkable effect of bitter melon peptide (mcIRBP-19) in patients with diabetes was also reported in the clinical study. This study summarized the scientific evidence of bitter melon peptides in regulating blood sugar levels through bioactive mechanisms. The bioactive peptides from bitter melon might open up new opportunities for the management of diabetes.

Insulin mimetic
Bitter melon contained a high dosage of 'plant insulin' [14] and effectively lowered blood sugar by reducing the speed of nephropathy development in streptozotocin (STZ)-induced diabetic rats [15], improving intestinal disorders caused by diabetes [16], enhancing the function of the intestine, and delaying development of cataracts [17]. Researches further indicated that bitter melon peptide had a hypoglycemic effect upon insulin-like biological activity and could regulate blood sugar to normal levels.

Copy@ Pang-Kuei Hsu
As shown in Figure 2, insulin binding to insulin receptor (IR) stimulated the auto-phosphorylation of IR, leading to the activation of phosphoinositide-3-kinase (PI3K) and Akt, the translocation of glucose transporter 4 (GLUT4), and the subsequent glucose uptake of adipocytes and skeletal muscle [18]. Lo   Hsu et al. [12] also indicated that bitter melon extract (contains mcIRBP-19) clinically regulated blood sugar levels in diabetes patients. After 12 weeks trials with a total of 142 subjects included in the study, results showed bitter melon peptide significant regulated the FG and HbA1c levels of patients. The findings provided the evidence that helps to verify the effectiveness of the bitter melon peptide in regulating diabetic patients' blood sugar levels, and gave a hint that bitter melon peptide has the high potential of oral plant insulin for the treatment of type 1&2 diabetes.

Conclusion
Epidemiological data revealed that type 2 diabetes required promising therapy to reduce the severe adverse effects of synthetic drugs. The bitter melon peptides with multiple mechanism could help to maintain the levels of blood sugar, such as inhibiting the enzymes like α-glucosidase and α-amylase, and insulin-mimetic activity from bioactive peptides (mcIRBP-68 and mcIRBP-19).
Recent studies also suggested that a regular intake of bitter melon peptides may benefit other human organ functions. Although the bitter melon peptides should not be used to replace the DM patient's medication, bitter melon peptides had the potential to the future applications of the anti-diabetic material of health food or drug development. Further chemical and pharmacological studies should be conducted to confirm its effectiveness.