Pharmacological Research Paper: Insulin

Introduction and Background

Since time immemorial, diabetic patients have encountered challenges controlling their blood sugar levels, mainly when they are not prepared for body reactions and hypertension. Insulin manages blood sugar levels with numerous health interventions to curtail diabetes mellitus or type 2. Historically, two German researchers, Joseph Von Mering and Oskar Mlinkowski, in 1889 ascertained that removing the pancreas from dogs developed symptoms of diabetes leading to death. The researchers concluded that the pancreases were the nerve center of insulin production. Furthermore, patients with diabetes mellitus or type 2 typically rely on insulin for treatment via injection. Briefly, insulin treatment reduces diabetes lethality by lowering blood sugar levels (converts glucose to energy) and storing excess glucose for energy. However, the asserted adverse reactions experienced by insulin, this paper seeks to explore causes of diabetes, insulin pharmacological roles, Pharmacodynamics, pharmacokinetics, side effects, and use of insulin treatment recommendations.

• Causes and Various Types of the Insulin Indication /Therapeutic Targets of insulin

When the protector fails to deliver or perform its duties in the body, the immune and entire body system is compromised. Similarly, Htwe (2021) notes that in case pancreatic cells fail or stop generating insulin, the glucose fails to enter the cell muscles for energy in the body. In turn, the glucose level hikes beyond normal, leading to sickness. Besides, when the body cells resist insulin, the pancreas is overpowered by body resistance, elevating glucose levels in the bloodstream. During pregnancy, hormones produced by the placenta increase body cell’s resistance to insulin, as much glucose remains in the bloodstream after pancreatic failure to generate insulin. Finally, some genes and viruses impair insulin production by triggering immune system attacks. Therefore, the above causes lead to either Type 1 or Type diabetes.

• Treatment Recommendations for Diabetes

Typically, prevention is better than cure. Non-pharmacologically, healthy eating that entails higher fiber foods such as non-starchy foods, vegetables, fruits, low-fat meals, healthy cooking oil, and a well-planned balanced diet is necessary for diabetic victims. Additionally, monitoring carbohydrates intake to stabilize blood sugar levels is compulsory during healthy eating (Omnigraphics, 2018). Regular physical exercise to maintain a healthy weight and regulate blood sugar levels. For example, aerobic exercise encompasses 30 minutes of walking or running and resistance exercise that enhances balance, strength, and energy to perform daily activities. For example, adults with diabetes mellitus should strive for three resistance exercises weekly to build flexibility and strength. Also, weight loss and regular blood sugar monitoring aid in maintaining the target body range.

Admittedly, diabetes medication such as metformin, Glumetza, and fortamet improve body sensitivity to insulin and lower glucose levels in the liver. Sulfonylureas help in insulin secretion such as glyburide and lower weight gain and blood sugar. Additionally, Glinides, a thiazolidinedione, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLTS inhibitors help lower the glucose level in the body, stroke, and heart attacks. Insulin therapy when blood sugar is not met (Mayo Clinic, 2019). Finally, diabetic patients should commit to managing the disorder by adhering to doctor’s health interventions and keeping the vaccination up to date.

• Pharmacological Aspects of the Recommended Treatment

a) Pharmacological class and indication

Insulin belongs to a class of hormones categorized into Rapid Acting-AnaLOGs such as lispro, glulisine, and Aspart. Improving adults’ pediatric patients and glycemic control with diabetes mellitus is indicated by human insulin. Short-Acting insulin includes regular (HumuLIN and NovoLIN), while intermediate Acting entails Protamine combined and NPH, and finally Long-Acting (Basal) are detemir (Levemir) and Glargine (Lantus). Occasionally, rapid-acting insulin has minute amino acids indicating fats absorption rate than the regular human insulin. They cover glucose excursions related to meals. NPH insulin has slow or delayed absorption for (90-120) minutes effectiveness.

The long-acting insulin has long action or duration (18-36) hours for steady point. Besides, animal insulin comprises beef and pork, hypurin neutral (porcine or bovine), protamine zinc, and isophane (Buryukova et al., 2017). The above insulin is extracted from slaughtered animals’ pancreases and purified to generate 200g pure insulin. The animal insulin is used because of hypoglycemia unawareness fear in patients. Lastly, human biphasic or mixed insulin, such as Insuman Comb 25. Humulin M3 and NovoMix 30 are commercially prepared with short-acting insulin. These insulin are rapid or soluble acting analogs and are usually administered daily before and after breakfast.

b) Pharmacodynamics and Mechanism of Insulin Action

Naturally, insulin is produced by beta cells of the pancreas. Spikes suspend insulin after meals in non-diabetic persons. When the body transit from post-absorptive to absorptive state, insulin spikes facilitate metabolic change. Hence, cellular glucose uptake is promoted by insulin in adipose tissues muscle, opposes catabolic energy stores, and enhances protein synthesis and DNA replication. Besides, amino acid stimulation by the liver promotes glycogenesis energy storage. Insulin triggers adipose tissue glycogenesis modifies glycolysis and various enzymes during the Krebs cycle. At the same time, insulin elevates growth by initiating growth hormone action such as DNA synthesis, cell division, and protein synthesis (Stubbs et al., 2017). Hence proinsulin as insulin precursor is transported by bet cells’ Golgi apparatus for packaging into granules. The proinsulin is made of 86 amino acids cleaved to C-peptide and insulin. The insulin molecule entails 51 amino acids arranged in both A and B chains linked by disulfide bonds.

The mechanism of insulin actions consists of glucose metabolism regulation in the body. Besides, insulin facilitates the amino acids and glucose uptake into adipose and muscle tissue except for the liver and brain. Anabolic insulin consists of fatty acid, glycogen, and protein synthesis stimulation. Although insulin represses liver glucogenesis, it binds with the receptor (IR), a heterotetrameric protein with trans-membrane beta and extracellular alpha units. IR receptor stimulates intrinsic tyrosine kinase activity after insulin binds to alpha subunits to the receptor of beta subunits (XINWEI, 2018). The bound receptor phosphorylates and auto-phosphorylate various intracellular substrates such as Cbl, Shc, receptor substrate proteins, APS, and Gab 1. Such coordinated activities activate molecular downstream signalings such as Akt and P13 kinase. Therefore, AKT regulates protein kinase C (PKC) and glucose transporter 4 (GLUT4) activities that play significant roles in catabolism and metabolism.

c) Pharmacokinetics (absorption, distribution, metabolism, and excretion)

Insulin pharmacokinetics comprise absorption. The distribution contains circulating insulin antibodies after binding to its receptors, degradation, and execration. Absorption commences after 30 minutes of insulin injection in the bloodstream as the lymphatic system plays a vital transportation role. The rate of insulin activity limits human insulin absorption in the bloodstream after subcutaneous absorption. Typically, there is inconsistent absorption variation correlated with blood flow in numerous injection sites. Patients are encouraged to inject the same body region. It should entail consistent insulin injection (Grant et al., 2021). Occasionally, abdomen preference as a preferred injection site is expected due to low susceptibility to adversely influencing insulin absorption. For example, insulin lispro, aspart, and glulisine have les daily in various body regions and absorption rates.

Factors affecting insulin absorption include injected area exercise such as limping for an hour, causing rapid absorption. Temperature speed absorption rate includes shower, hot bath, and sauna immediately after injection. Injection sites such as the abdomen enhance fast absorption, and larger insulin doses entail prolonged action and duration. On the other hand, insulin distribution is another factor related to its resistance, especially in chronic disorders. The in vivo insulin action leads to signal blockage or mobilization cascade in insulin-sensitive regions or tissues such as adipose tissue, liver, and skeletal muscle (Mayo Clinic, 2019). Therefore, insulin cascades its pathways from pancreatic islets via sensitive receptors due to fenestrated endothelium, leading to immediate insulin distribution. The barriers to insulin mechanism action on skeletal muscles are associated with access to blood-borne nutrients, glucose access, and receptors to the consuming tissues.

Metabolically, the blood flow distribution pattern limits glucose access to organ or tissue metabolism in case of a high glucose transport rate across the endothelium, the metabolic access substrate, and hormone to skeletal muscles cells. Orally inhaled human insulin is metabolically compared with regular human insulin leading to energy release. Conversely, the liver and kidney play a significant role in excerpting insulin as the liver degrades (50-60) in the portal vein. Immediately after insulin injection, the kidney degrades insulin before reaching the portal vein. In turn, renal dysfunction decreases insulin clearance and delays its impacts on exogenous and endogenous insulin production.

d) Side effects and adverse effects

Insulin therapy causes weight gain, swelling of legs and arms, and low blood sugar (hypoglycemia), leading to hunger, shakiness, sweating, and dizziness. Injected site swells, itch and becomes red while the skin changes to a lipodystrophy condition. The severe side effects encompass sleepiness, delirium or confusion, mood changes, anger, sadness, stubbornness, mood changes, headaches, impaired vision, fatigue, and dizziness (Stubbs et al., 2017). Hypokalemia or low blood potassium is accompanied by weakness, constipation, tiredness, heart rhythm, and breathing problems. Finally, severe allergic reactions cause sweating, faintness, high heart rate, and rashes.

e) Contraindication

Although insulin is prioritized to category B pregnancy, especially diabetes mellitus, insulin association is coincidental due to perinatal morbidity, hyperglycemia, and numerous congenital malformations. Likewise, insulin-dependent women produce milk with high nitrogen and lower lactose leading to low milk intake by the infant.

f) Therapeutic Consideration

The health care provider should foster awareness of insulin and its impact on blood glucose by encouraging victims to prioritize self-monitoring plans, physical exercise, a healthy diet, and recommendations for insulin titration after initiation. Diabetic care in aging is becoming complicated regarding physiological and psychological alteration of aging.

Conclusion

In summary, diabetic management strategies should be based on insulin’s causes, Pharmacodynamics, pharmacology, and pharmacokinetics for more straightforward intervention implementation that minimizes side effects. Besides, improving adults’ pediatric patients and glycemic control with diabetes mellitus is indicated by human insulin. The adverse effects of insulin injection require an amicable intervention on manufactured drugs and therapies to minimize side effects. Finally, regular physical exercise, maintaining a healthy body weight, and monitoring the glucose level should be accompanied by a teaching session that encourages and motivates victims to decrease depression and anxiety.

References

Buryukova, E. V., Jabbar, A., & Elizarova, S. V. (2017). When basal insulin is not enough: successful strategies for insulin intensification in patients with type 2 diabetes mellitus. Diabetes Mellitus, 20(5), 363–373. https://doi.org/10.14341/dm8824

Grant, M., Heise, T., & Baughman, R. (2021). Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus. Clinical Pharmacokinetics. https://doi.org/10.1007/s40262-021-01084-0

Htwe, T. N. (2021). Metabolic Risk Markers in Insulin Resistance and Non-Insulin Resistance Type 2 Diabetes Mellitus. SOJ Diabetes and Endocrinology Care, 1(2). https://doi.org/10.53902/sojdec.2021.01.000508

Mayo Clinic. (2019). Type 2 diabetes – diagnosis and treatment. Mayoclinic.org. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199

Omnigraphics, I. (2018). Diabetes sourcebook : basic consumer health information about type 1 and type 2 diabetes, gestational diabetes, and other types of diabetes and prediabetes, with details about medical, dietary, and lifestyle disease management issues, including blood glucose monitoring, meal planning, weight control, oral diabetes medications, and insulin ; along with facts about the most common complications of diabetes and their prevention, current research in diabetes care, tips for people following a diabetic diet, a glossary of related terms, and a directory of resources for further help and information. Omnigraphics, Inc.

Stubbs, D. J., Levy, N., & Dhatariya, K. (2017). Diabetes medication pharmacology. BJA Education, 17(6), 198–207. https://doi.org/10.1093/bjaed/mkw075

XINWEI, H. (2018). The Impact of Different Initial Insulin Dose Regimens in Short-Term Intensive Insulin Therapy. Diabetes, 67(Supplement 1), 1054-P. https://doi.org/10.2337/db18-1054-p