What question did this study set out to answer?

To determine how molecular aggregation state influences subcutaneous insulin absorption rates and elucidate the mechanism behind conventional soluble human insulin absorption.

November 1, 1991Diabetes Care

Subcutaneous Insulin Absorption Explained by Insulin's Physicochemical Properties: Evidence From Absorption Studies of Soluble Human Insulin and Insulin Analogues in Humans

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To determine how molecular aggregation state influences subcutaneous insulin absorption rates and elucidate the mechanism behind conventional soluble human insulin absorption.
Conducted a single-blind randomized comparison in 7 healthy male volunteers (aged 22–43 years) across four test days spaced one week apart.
Injected equimolar subcutaneous doses (0.6 nmol/kg) of 125I-labeled hexameric soluble human insulin, dimeric analogue AspB10, mixed monomer/dimer AspB28, and monomeric analogue AspB9, GluB27.
Monitored absorption kinetics via external gamma-counting to measure residual radioactivity at the injection site over time.
Initial fractional disappearance rates were 20.7 ± 1.9%/h for hexameric human insulin, 44.4 ± 2.5%/h for dimeric AspB10, 50.6 ± 3.9%/h for AspB28, and 67.4 ± 7.4%/h for monomeric AspB9, GluB27 (dimer vs. hexamer, P < 0.001; monomer vs. dimer, P < 0.01).
Initial disappearance rates showed a strong inverse linear correlation with insulin association state (r = -0.98, P < 0.02), with only the monomer exhibiting a continuous monoexponential absorption course (73.3 ± 6.8%/h).
Multi-state formulations absorbed in distinct accelerating phases: dimeric insulin rose from 44.4 ± 2.5%/h (0–2 h) to 68.9 ± 3.5%/h (from 2.5 h onward), while hexameric insulin progressed across three phases from 20.7 ± 1.9%/h (0–2 h) to 45.6 ± 5.0%/h (2.5–5 h) and 70.6 ± 6.3%/h (from 5 h onward).

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Implication

Randomized trial demonstrates that molecular aggregation state dictates subcutaneous insulin absorption rates in healthy adults, indicating self-association drives the initial absorption lag.

Cite This Study

Kang et al. (1991) studied this question.

synapsesocial.com/papers/6a72c0e6ce524a4339c58fc2 https://doi.org/10.2337/diacare.14.11.942

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Implication

Randomized trial demonstrates that molecular aggregation state dictates subcutaneous insulin absorption rates in healthy adults, indicating self-association drives the initial absorption lag.

Subcutaneous Insulin Absorption Explained by Insulin's Physicochemical Properties: Evidence From Absorption Studies of Soluble Human Insulin and Insulin Analogues in Humans

Key Points

Discussion

Implication

Cite This Study

Subcutaneous Insulin Absorption Explained by Insulin's Physicochemical Properties: Evidence From Absorption Studies of Soluble Human Insulin and Insulin Analogues in Humans

Key Points

Discussion

Implication

Cite This Study