# RKS: INSULIN – THE KEY FOR DIABETES LOCK

ENJOY PILL LIFE & NOT PRICK LIFE!

RKS / 2026-2027 / Ser 9 / Blog 6

1st September 2026

MOST DIABETICS ARE NOT DEFICIENT INSULIN

FUNCTIONAL INSULIN KEEPS DIABETES AT BAY

Dear Reader,

Although diabetes was first recorded in the ancient Egyptian Ebers Papyrus around 1552 BCE it was only in 1889 that German scientists Joseph von Mering and Oskar Minkowski were credited relating the disease with pancreatic secretion. However, it was Belgian investigator de Meyer (1909) and also a British researcher Schaefer (1916) who proposed the name “insuline” for this hormone manufactured by pancreas.
Diabetes is usually equated by less insulin by most but the fact is it is defective insulin working in most cases. 90% of patients have Type 2 Diabetes Mellitus (T2DM) and the goal of treatment lies in not giving insulin but in increasing the functioning (or sensitivity) of insulin. On the other hand, T1DM is hereditary and occurs because of failure of pancreas to manufacture insulin.
The focus of the blog is to imprint in our minds that most of the diabetics are of T2DM category and they, at least for many decades, have more than plentiful circulating insulin in blood. The problem for T2DM lies in insulin’s defective functioning and information regarding the same is very crucial to fathom how one can best address T2DM.

INSULIN BASICS

The role of insulin is primarily to keep the blood glucose within the normal range of 70-100 mg/dL. If it fails to do so, either one has pre-diabetes or is a diabetic patient.

The God-given blessing is pancreas scale up insulin production whenever blood glucose is higher as in a diabetic or a prediabetic. This higher than normal insulin fasting levels is hyperinsulinemia which is defined as:

Early hyperinsulinemia: Plasma concentrations 10-15 mIU/mL

Definite hyperinsulinemia: Plasma concentrations >25 mIU/mL

Thus, the body makes its full attempt to get rid of excess glucose and, if unsuccessful in its attempt, pre-diabetes of T2DM is the consequence.

INSULIN MECHANISM

Excess glucose, over and above the normal blood concentrations, enters the beta-cells in pancreas and is metabolized to adenosine triphosphate (ATP).
ATP opens calcium (Ca++) channels to open in beta-cells.
Ca++ influx through the Ca++ channels stimulate the vesicles which store insulin to release the hormone in response to glucose trigger [Glucose-Stimulated Insulin Secretion (GSIS)].
Receptors of insulin (IR) are predominantly present on muscle cells (myocytes), hepatocytes (liver cells) and fat tissue cells (adipocytes).
The excess insulin released as a result of GSIS binds with insulin receptors (IR).
The lock and key interaction between insulin and IR triggers a chain reaction within the myocytes adipocytes.
Signals are generated within the cell (intracellular) and specialized proteins transporters called GLUT4 (glucose transporters) move the cell's outer membrane and create gaps.
The glucose leaves the bloodstream and enters the various target cells to be used for ATP manufacturing.

INSULIN TARGET TISSUES

The intent of insulin is to ensure all the meal-derived glucose that has entered in blood should be pushed into cells and tissues. However, there are 2 types of tissues:

Insulin-Dependent Tissues: Muscles (70-80% of glucose) and fat cells (0-10% of glucose) require insulin for glucose to enter.
Insulin-Independent Tissues: 20-30% of blood glucose enters organs like the brain, nerves and liver but do not require insulin for its uptake.

If the insulin is not able to efficiently remove all the glucose of food that has entered the blood within 2-3 hours of consuming meals it is referred to as insulin resistance – meaning insulin has lost its sensitivity (ability) to deal with blood glucose efficiently.

INSULIN RESISTANCE

The only defect that can hinder insulin functioning is when it is unable to interact with IR and bind with it tightly akin to key insertion in keyhole of a lock. The fasting levels of insulin are indicative of insulin resistance.

Fasting Glucose: Optimal levels are typically <100 mg/dL.
Fasting Insulin:

Optimal levels are usually <8.5 mIU/mL, with metabolic experts often aiming for <5 IU/mL.
Borderline / Early resistance: 8.5-10 mIU/mL
Moderate / Significant resistance: >10-25 mIU/mL

Insulin resistance is typically graded using the HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) score.

GRADING INSULIN RESISTANCE

HOMA-IR score vs insulin sensitivity / resistance:

Grade 0 – Optimal sensitivity: HOMA-IR <1.0
Grade 1 – Normal sensitivity: HOMA-IR 1.0-1.9
Grade 2 – Early / Mild resistance: HOMA-IR 2.0-2.9
Grade 3 – Significant / Moderate resistance: HOMA-IR 3.0-4.9
Grade 4 – Substantial / Severe resistance: HOMA-IR >5.0

Hence, in a normal individual (nondiabetic / non-prediabetic), sans insulin resistance, the fasting plasma insulin concentrations always are below 8.5 mIU/mL.

2 hours post-meals the amount of insulin in blood can measure between 18-166 mU/mL in a normal non-pre-/diabetic individual vs >166 mU/mL in T2DM. However, the level eventually returns back to within normal range in those whose insulin sensitivity is maintained but in the prediabetic and diabetic individuals, the baseline concentrations remain high and this constitutes insulin resistance.

DIAGNOSING INSULIN RESISTANCE

C-Peptide is a by-product released into the bloodstream in equal amounts to insulin as the pancreas produces it. Because it stays in the blood longer than insulin, a C-Peptide Test is used to accurately measure how much insulin the body is making naturally.

Normal C-Peptide (0.5-2.0 ng/mL): Pancreas produce the required amounts of insulin which are effective in facilitating glucose uptake by target tissues.
Low C-Peptide (<0.5 ng/mL): In late-stage T2DM pancreas struggle to produce insulin and also in T1DM wherein insulin production is virtually non-existent. In T2DM, which constitutes 90% of diabetes incidence, the low C-Peptide is because the blood glucose has not been kept under tight check and the pancreatic beta-cells over years have got exhausted in keeping up with higher demands over the decades.
High C-Peptide (>2.0 ng/mL): To overcome insulin resistance body is makes excess insulin which is reflected in the high C-Peptide levels. This is the most common scenario seen in prediabetes as well as in those T2DM who have not reached the stage of beta-cell exhaustion.

There are 250 million to 1 billion beta-cells and only when >75% of these are destroyed hyperglycemia results since the pancreas can no more cope with the glucose levels in blood exceeding normal range. In most Asians, beta-cell reserves are depleted by ~50% at the time of diagnosis, absolute depletion of insulin production typically takes 2 to 8 years later and then necessitates insulin jabs for T2DM individuals.

MANAGING INSULIN RESISTANCE

For optimizing insulin functioning there are two mechanisms:

Ensure the IRs are accessible.
Facilitate the tight binding of insulin with IR so as to trigger the required intracellular signaling mechanism for allowing glucose entry into the target cells for its utilization for ATP production.

INCREASING CELL MEMBRANE FLUIDITY

If the insulin has to interact with IR, naturally the latter must be easily accessible and hence be superficially present right on surface of the cell wall.

Fig: A floating vs sunken object depiction for understanding positions of IRs.

It is but logical that, if the IR is sunk to the bottom of the cell wall the insulin cannot interact when it reaches the target cell since receptor is not accessible since it is drowned in the cell membrane. Omega-3 fatty acids are best bet to keep the IR floating primarily because of eicosapentaenoic acid (EPA). The fluidity of a membrane is dictated by the ratio of cholesterol vs the phospholipid (PL) molecules present – PL is fluidizing whilst cholesterol is rigidizing for cell wall.

Fig: Cell membrane structure.

The ideal normal Cholesterol-to-Phospholipid (Chol/PL or C/PL) molar ratio for a healthy human plasma membrane ranges between 0.5 and 1.0.

High concentrations of cholesterol can even cause the formation of immiscible cholesterol domains or crystals. Hence, when the C:PL ratio spikes (e.g., beyond 1.0), the membrane becomes excessively rigid and viscous. EPA enhances by fluidity by reducing the size and formation of rigid cholesterol-crystalline domains by up to 65.5%. This makes the IR more likely to float, rather than sink to bottom of cell wall, and hence allows insulin to interact with the receptor and trigger chain of events leading to glucose uptake.

INSULIN & IR TIGHT BINDING

Glucose Tolerance Factor (GTF) is an organic chromium complex that acts as a physiological enhancer of insulin activity. By binding to IRs, GTF increases the receptor's affinity for insulin, which improves cellular responsiveness and helps the body efficiently clear glucose from the blood. Chromium supplementation can increase the number of active IRs on cell surfaces and improve the binding affinity of insulin to these receptors.

Chromodulin (an oligopeptide) is present in all insulin-sensitive cells and occurs in two forms.
Chromium binds with free apochromodulin within the myocytes and adipocytes and hepatocytes.
When the four trivalent chromium ions bind tightly with apochromodulin it is transformed to active holochromodulin.
The holochromodulin binds to IR and wakes up the enzyme tyrosinase present in the receptor part that is submerged within the target cell.
Tyrosinase kinase activates PI3K (phosphoinositide 3-kinase) which is present in cytoplasm and close to inner surface of cell membrane.
PIP2 (phosphatidylinositol 4,5-bisphosphate) is a lipid present in cell membrane. When PI3K is activated it converts PIP2 to PIP3 (phosphatidylinositol 3,4,5-triphosphate).
PIP3 creates a docking site for Akt (protein kinase B) enzyme present in cell membrane.
Activated Akt signals the release of GLUT4 storage vesicles (GSVs) present in cytoplasm.
GSVs are the container whose cargo is GLUT4. When GSVs are stimulated they move and merge with cell membrane and GLUT4 within these create holes or gaps for facilitating glucose in blood to enter the target cell.

Fig: Insulin and IR interaction and glucose uptake sequential triggers.

Summarizing, chromium complex moves into the cell to amplify the signal, driving the translocation of GLUT4 transporters to the cell membrane. This allows the cell to pull glucose out of the blood more efficiently, ultimately lowering HOMA-IR.

CONCLUSION

Insulin resistance is a harbinger of T2DM and its primary reasons include:

Excess body weight (especially belly fat)
Physical inactivity
Family history of T2DM
Age 35 years and older
PCOS (polycystic ovary syndrome)
Sleep apnea

T2DM is undeniably one of the greatest healthcare challenges worldwide, fuelled by an escalating global prevalence that exceeds 800 million cases. It operates as a silent epidemic driving severe complications like heart disease, kidney failure, blindness, paralysis and amputations, placing unsustainable burdens on both patients and family members. India is widely considered the "Diabetes Capital of the World" due to its staggering burden of the disease, with an estimated 212 million adults living with diabetes and pre-diabetes. South Asians naturally have higher insulin resistance and are more prone to storing visceral fat (fat around the belly and organs), which severely drives up diabetes risk.

Regular consumption of nutraceuticals like omega-3 fatty acids and chromium can facilitate insulin binding to IR and maintain insulin sensitivity. Besides, exercising also fights insulin resistance which is only inevitable as one piles on years. Exercise lowers insulin resistance primarily by stimulating muscle contraction. Following exercising the myocytes are forced to absorb and use glucose independently of insulin. Consistent physical activity also improves insulin sensitivity by increasing muscle mass, enhancing cellular energy pathways, namely, adenosine monophosphate – activated protein kinase (AMPK). AMPK is present in sarcoplasm as well as nucleus of myocytes. Whilst exercising the ATP stores deplete and AMP or adenosine diphosphate (ADP) spikes to activate the AMPK present. The latter then tiggers GSVs relocation to cell membrane resulting in GLUT4-mediated pores formation and glucose uptake by the muscles.

Since 1 in 3 Indians is already at risk, or is having diabetes endeavor to fight insulin resistance by exercising and regular consumption of beneficial nutraceuticals.

Save your nerves.

Save your heart.

Save your brain.

Save your eyes.

Save your limbs.

Save your kidneys.

Save your Quality of Life (QoL).

Timely.

DR R K SANGHAVI

Prophesied Enabler
Experience & Expertise: Clinician & Healthcare Industry Adviser

-------------------------------------------------------------------------------------

POWERED BY -

# fuzionnutra.com

Search This Blog

Dr R K Sanghavi