You have provided an extensive and detailed overview of glucose metabolism, insulin, its pathophysiological alterations, and related interventions. Before I comment, it's essential to note that anyone considering the use of insulin or any medical intervention should always consult with a healthcare professional. Using insulin inappropriately can be dangerous and life-threatening.

Insulin and Glucose Metabolism

  1. You are accurate in your description of how insulin is secreted in response to elevated blood glucose levels and how it acts to facilitate glucose uptake into the cells.
  2. The HOMA-IR is indeed a widely accepted and utilized method for determining insulin resistance in clinical settings. It combines both fasting insulin and glucose levels to give a measure of how well the body's insulin is functioning.
  3. Glucagon plays an essential role in glucose metabolism by acting as an antagonist to insulin. It stimulates the release of glucose from the liver and promotes gluconeogenesis.

Insulin Resistance and Type 2 Diabetes

  1. The development of insulin resistance is multifactorial, and while over-nutrition and obesity are primary causes, genetics, inactivity, inflammation, and other factors also play a role.
  2. The relationship between obesity and insulin sensitivity is complex. While obesity is a risk factor for insulin resistance, not all obese individuals are insulin resistant. Moreover, lean individuals can also be insulin resistant.

Interventions to Improve Insulin Sensitivity

  1. Metformin, Berberine, and thiazolidinediones (like pioglitazone) are drugs used to treat type 2 diabetes that act through different mechanisms to improve insulin sensitivity.
  2. Several supplements and natural compounds like alpha-lipoic acid (ALA) and chlorogenic acid are being researched for their potential benefits in improving insulin sensitivity.

Exogenous Insulin

  1. Exogenous insulin can be a life-saving drug for those with type 1 diabetes and some with advanced type 2 diabetes.
  2. It's crucial to underscore the potential dangers of exogenous insulin use, especially when used outside a medical context. Inappropriate dosing can lead to hypoglycemia, which can be fatal.
  3. Bodybuilders and athletes sometimes use insulin for its anabolic effects, but this comes with significant risks.

In summary, the intricate dance of glucose metabolism, insulin, and related hormones is crucial for human survival. Insulin resistance and type 2 diabetes are increasing globally, leading to various interventions aimed at improving insulin sensitivity. Anyone considering interventions, especially those involving exogenous insulin, should consult with a healthcare professional to ensure their safety and appropriateness.