(Author’s affiliation)
Diabetes is a polygenic disease characterized by significantly higher levels of glucose in the blood. In this disorder, metabolic disorders lead to persistent thirst (polydipsia) and excessive level of urination (polyuria). Diabetes is caused by insulin-related disturbances in the body. In healthy human beings, pancreatic β cells have insulin that is found as a hexamer having three insulin dimers attached together by two central zinc ions. The insulin monomer has a 21-residue A chain as well as a 30-residue B chain. These chains are cross-linked by two disulfide bridges, i.e. CysA20-CysB19 and CysA7-CysB7. There is also a 3rd disulfide linkage within A chain, i.e. CysA6-CysA11. It has been found that the conversion of insulin hexamer to insulin monomer is important for its bioavailability1, and normal functioning.
Presently, 383 million people from around the world are living with diabetes mellitus. Diabetes mellitus is of two types, i.e. type 1 diabetes and type 2 diabetes. Type 1 diabetes is considered as an autoimmune disease in which β cells are progressively destroyed leading to polydipsia, polyuria, hyperglycemia, and weight loss. Type 2 diabetes is caused by a combination of disturbed insulin secretion and insulin resistance. Obesity, poor diet, and low level of activity are involved in the development of this type of diabetes2. Diabetes mellitus is diagnosed with the help of glucose level in the blood that is abnormally high. In this condition, plasma glucose level and fasting plasma glucose level are checked. After diagnosing the diabetic condition in the patient, it is usually confirmed by checking the plasma glucose one more time. Usually, diabetes is diabetes mellitus but there is another kind of disease, known as diabetes insipidus that has almost similar symptoms to that of diabetes mellitus but shows no disturbances in the metabolism of sugar. In diabetes insipidus, voiding of dilute urine may exceed 3 liters per day, even when the patient faces water deprivation. Diabetes insipidus is usually caused by severe head trauma, tumors, inflammation, autoimmune disorders, infections such as meningitis and toxoplasmosis, and genetic mutations3. If diabetes is not properly managed and/or treated, it could lead to macrovascular and microvascular complications such as blindness, kidney failure, cardiovascular diseases, and amputation2. Different types of therapeutic and management strategies are available for the diabetes4.
Management of diabetes and its efficient therapeutic interventions usually help in the prevention, delay, or remission of diabetes. These therapeutic strategies may range from population-wide strategies dealing with energy balance to targeted individual strategies for the prevention of progression to the disorder. Population-wide strategies target the whole population and these strategies are successfully implemented by community and/or regulatory interventions. These interventions work on the alteration of the environment with unhealthy behaviors to an environment with healthy behaviors. Strategies for the prevention of diabetes at an individual level usually involve the individual factors such as patient history, lifestyle interventions, and heredity4.
Type 1 diabetes has no known preventive measure, whereas type 2 diabetes could be prevented or delayed. In case of type 1 diabetes mellitus, non-endogenous insulin is required by the patient. In case of type 2 diabetes, lifestyle interventions could be of sufficient help2. Treatment of diabetes insipidus may include the use of intravenous glucose solution or the injection of dDAVP along with pure water. dDAVP is a synthetic vasopressin analog having more antidiuretic properties and fewer vasopressive properties. Desmopressin may also be used for the treatment of diabetes insipidus. In order to treat, nephrogenic diabetes insipidus, which is caused by resistance to vasopressin, water supplementation is required. Moreover, modification of the renin-angiotensin system with the help of angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists could also be done to deal with the problem of diabetes insipidus3.
A study from Australia shows that in spite of the best practices to control and treat diabetes, prevalence of diabetes would keep on increasing in the future years4. It has been reported that the number of people living with diabetes would increase by more than 50% over the next two decades. Moreover, researchers have found that most of the monotherapeutic treatments fail to give required outcomes within 3 years. This problem leads to increased chances of morbidity and mortality as a result of diabetes. On a further note, sometimes inappropriate and improperly researched treatment options can result in increased chances of hypoglycemic events in the patients of diabetes 2.These findings are showing that more studies are required to find novel therapeutic strategies for controlling diabetes on large scale.
Animal venoms have been found to be novel and efficient therapeutic tools for various disorders. Usually, venoms have small proteinaceous components that are highly stable in various conditions including extracellular environment. They are not only stable in nature, but they are also highly specific for their physiological target and show a good level of bioavailability. The U.S. Food and Drug Administration (FDA) has also approved several venom-derived therapeutics 1.
A recent study shows that venom obtained from one of the species of marine cone snail, Conus geographus, could provide significant help in the development of efficient therapeutic strategies for the management of diabetes. The snail uses insulin-based venom to trap the prey. The prey keeps on moving through the invisible trap and finally stops moving as a result of the development of severe hypoglycemic state caused by the venom. Researchers noted that this venom could help in developing ‘ultra-fast-acting’ insulins. Human insulins have specific components that are important in making connections of insulin and receptors. Researchers worked on the three dimensional structure of snail venom, and found that the cell signaling process as well as the connection of insulins with receptors in human beings could be accelerated with the help of the venom. Researchers noted that the cone snail insulin could initiate the cell signaling pathways in human beings; therefore, it could be used to bind to human receptors1.
Figure 1: Human insulin and human insulin receptor (Source: Walter+Eliza Hall, Institute of Medical Research)
Hypothesis: Snail produced venom could help in both type 1 diabetes and type 2 diabetes in all ages.
First aim of performing the study is to know the efficacy of snail venom in both type 1 diabetes and type 2 diabetes in all ages. In the study, researchers have not clearly discussed the efficacy of the venom in both types of diabetes. Moreover, the study is not showing the efficacy of venom in people of different ages.
Second aim of the study is to know whether the venom has only insulin-based components or it can also work on other body parts such as kidneys and leading to excessive voiding of urine and hypoglycemia. This aim could help in knowing the efficacy of venom in dealing with diabetes insipidus.
References
1. Menting, J. G.; Gajewiak, J.; MacRaild, C. A.; Chou, D. H.-C.; Disotuar, M. M.; Smith, N. A.; Miller, C.; Erchegyi, J.; Rivier, J. E.; Olivera, B. M., A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin. Nature Structural & Molecular Biology 2016, 23, 916-920.
2. Kleinberger, J. W.; Pollin, T. I., Personalized medicine in diabetes mellitus: current opportunities and future prospects. Annals of the New York Academy of Sciences 2015, 1346 (1), 45-56.
3. Leroy, C.; Karrouz, W.; Douillard, C.; Do Cao, C.; Cortet, C.; Wemeau, J. L.; Vantyghem, M. C., Diabetes insipidus. Annales d'endocrinologie 2013, 74 (5-6), 496-507.
4. Backholer, K.; Peeters, A.; Herman, W. H.; Shaw, J. E.; Liew, D.; Ademi, Z.; Magliano, D. J., Diabetes prevention and treatment strategies are we doing enough? Diabetes care 2013, 36 (9), 2714-2719.
