Human IGF-I CAS 67763-96-6

Molecular mechanism of islet hormone resistance (hIGF-I intervention targets):Insulin resistance (IR) is the common pathological basis of metabolic syndrome, type 2 diabetes, obesity and fatty liver. The core mechanism is:Lipotoxicity: elevated FFA → muscle/liver lipid deposition → IRS1/2 serine phosphorylation → impaired insulin signaling;Inflammatory stress: obesity → inflammation of adipose tissue → elevation of TNF - α and IL-6 → inhibition of islet hormone signaling;Post receptor defects: decreased IR expression, insufficient tyrosine phosphorylation, and impaired GLUT4 translocation.Multi target mechanism of human IGF-I improving IR.

Bypass insulin resistance IR and directly activate key metabolic signaling cascades (specific receptor replacement effect)-Mechanism: Recombinant hIGF-I directly activates downstream PI3K/Akt signaling via IGF-1R/heterozygous hybrid receptors, without fully relying on impaired IR physiological function; In patients with severe persistent IR resistance, intact IGF-1R signaling pathway is stably retained, which can effectively compensate insufficient insulin function; Experimental evidence: In IR gene knockout (IR ⁻/⁻) model mice.

Anti lipolysis → FFA release reduced by 60% -80% → muscle/liver lipid deposition reduced → IRS1/2 serine phosphorylation reduced, tyrosine phosphorylation restored → blood glucose-lowering peptide signaling repair;Enhanced fatty acid oxidation → Accelerated muscle fat clearance → Improved lipotoxicity → Increased insulin sensitivity.Anti inflammatory and antioxidant ;Inhibition of inflammatory factors: reduce the expression of TNF - α and IL-6 in adipose tissue, and decrease the inhibition of islet hormone signaling by inflammation.

Improve fat distribution:promote subcutaneous fat synthesis, inhibit visceral fat proliferation → reduce visceral fat area by 20% -30% → reduce inflammation, decrease lipotoxicity, and increase insulin sensitivity.Clinical effects: Improvement of insulin resistance related diseases;Type 2 diabetes: after 12 weeks of treatment with rhIGF ‑ I (50 – 80 μ g/kg/day), insulin sensitivity increased by 40% – 60%, HbA1c decreased by 0.8% – 1.2%.

Metabolic syndrome: waist circumference reduced by 3-5 cm, blood pressure decreased by 5-8 mmHg, TG decreased by 30%, HDL increased by 15%.

Type 2 diabetes (T2DM): reduce blood sugar, improve resistance, and protect beta cells

Lowering blood sugar: promoting muscle glucose uptake, inhibiting hepatic gluconeogenesis, and reducing hepatic glucose output;

Improving resistance: reducing lipotoxicity, anti-inflammatory, repairing insulin signaling;

Protecting beta cells: inhibiting apoptosis, promoting proliferation, and maintaining blood glucose-lowering peptide reserves.

Applicable population: T2DM patients with severe blood glucose-lowering peptide resistance, large blood glucose fluctuations, high insulin dosage, and comorbidities of obesity/fatty liver;Efficacy: After 6 months of rhIGF-I combined with insulin treatment, HbA1c decreased from 8.5% to 7.2%, blood glucose-lowering peptide dosage decreased by 25%, and the incidence of hypoglycemia decreased by 50%;Advantages: No weight gain, improved blood lipids, cardiovascular protection, superior to traditional hypoglycemic drugs.Type 1 diabetes (T1DM): reduce blood sugar fluctuation, improve blood lipids and protect blood vessels:T1DM patients have absolute blood glucose-lowering peptide deficiency, decreased IGF-I levels, lipid metabolism disorders, and a high risk of vascular complications; human IGF-I assists in lowering blood suga.

The combination of rhIGF-I and blood glucose-lowering peptide therapy for T1DM resulted in a 30% decrease in blood glucose standard deviation, a 0.5% -0.8% decrease in HbA1c, a 25% decrease in TG, a 12% increase in HDL, and a delayed progression of retinal lesions.Non alcoholic fatty liver disease (NAFLD): reduces liver fat, improves inflammation, and delays fibrosis:Inhibit hepatic lipid synthesis, promote fatty acid oxidation, reduce FFA uptake → decrease hepatic lipid deposition.

Obesity and metabolic syndrome: weight loss, improvement of abdominal obesity, regulation of blood lipids and blood pressure.

Inhibit visceral fat, promote subcutaneous fat, reduce lipotoxicity, improve blood glucose-lowering peptide resistance, and anti-inflammatory.After 6 months of rhIGF-I treatment, patients with metabolic syndrome experienced a weight loss of 4.2 kg, waist circumference reduction of 4.5 cm, blood pressure reduction of 6/4 mmHg, TG reduction of 32%, and HDL increase of 14%.

Exercise induced human IGF-I: Natural Muscle Enhancement Signal Driven by Mechanical Tension:Resistance training (strength training) and high-intensity interval training (HIIT) induce a large amount of local hIGF-I synthesis in skeletal muscles through mechanical tension, muscle micro injury, and metabolic stress, which are the core endogenous mechanisms for increasing muscle mass and improving physical fitness during exercise.Mechanical tension (core trigger): Muscle tension/compression generated by high load resistance training (such as squats and bench presses) activates IGF1 gene transcription through the integrin FAK-ERK pathway, and local hIGF-I concentration peaks 24-48 hours after training, continuously driving MuSCs activation and muscle fiber hypertrophy.

Training intensity specificity: The hIGF-I levels induced by extreme load (5-10 exhausts) are 2-3 times higher than those induced by moderate load (15-20 exhausts); Eccentric contraction (such as squats and bench presses) induces more hIGF-I and has a more significant muscle building effect than centripetal contraction;Individual differences: Individuals who are young, have high testosterone levels, and have more muscle mass tend to have a greater increase in hIGF-I levels after exercise; Elderly, sedentary, and obese individuals have delayed hIGF-I response and poor muscle building effects.The synergistic effect of hIGF-I and exercise muscle building: amplifying the training effect.

Exogenous supplementation of rhIGF-I in combination with resistance training can amplify muscle building effects, accelerate recovery, and improve physical fitness, especially suitable for muscle bottleneck periods, elderly fitness, and physical fitness enhancement.Magnifying muscle building effect: The increase in muscle mass in the exercise+rhIGF-I group was 1.5-2 times that of the pure exercise group, with a more significant increase in muscle fiber diameter and faster improvement in strength;Recovery acceleration: rhIGF-I promotes micro injury repair, reduces inflammation, alleviates delayed onset muscle soreness (DOMS), shortens recovery time, and increases training frequency.

Physical fitness improvement: rhIGF-I increases the proportion of type II fast muscle fibers, enhances explosive power, increases endurance, and reduces fatigue, suitable for athletes in strength, speed, and endurance events.Long acting analogues (IGF-I LR3, DES): clinical and exercise applications:Natural hIGF-I has a short half-life (12-15 hours) and requires frequent injections.

IGF-I LR3 (Long R3 IGF-I): N-terminal deletion of 3 amino acids+Arg substitution for Glu, half-life extended to 20-30 hours, reduced binding affinity with IGFBP-3, increased free active form, strong systemic effect, used for sarcopenia, cachexia, and systemic muscle enlargement;

IGF-I DES (1-3 IGF-I): N-terminal deletion of 3 amino acids, half-life of about 6 hours, local activity 10 times higher than natural hIGF-I, used for local muscle repair, shaping, and small muscle group muscle enlargement.