Factors Influencing the Absorption, Serum Insulin Concentration, and Blood Glucose Responses After Injections of Regular Insulin and Various Insulin Mixtures

Galloway, John A.; Spradlin, C T; Nelson, Roger; Wentworth, Samuel M.; Davidson, Jaime A.; Swarner, J L

doi:10.2337/diacare.4.3.366

Cited by 229 publications

(137 citation statements)

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“…For example, some studies have reported slower insulin absorption and decreased glucose-lowering effects of short-acting insulins when injected SC in the thigh than in the abdomen [4][5][6][7][8] or deltoid [4,5]. The same finding has also been observed following administration of regular human insulin or neutral protamine Hagedorn (NPH) insulin in the thigh, compared with injection in the abdomen [7].…”

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Glucose-lowering Effect of Insulin Degludec is Independent of Subcutaneous Injection Region

Nosek¹,

Coester²,

Thomsen³

et al. 2012

Canadian Journal of Diabetes

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Section: Discussionmentioning

confidence: 79%

“…However, differences can exist in the pharmacokinetic and pharmacodynamic properties of insulin following subcutaneous (SC) administration in different regions [4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Glucose-lowering Effect of Insulin Degludec is Independent of Subcutaneous Injection Region

Nosek¹,

Coester²,

Thomsen³

et al. 2012

Canadian Journal of Diabetes

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“…However, due to the sustained absorption, insulin concentrations between meals may be inappropriately high which commonly results in episodes of hypoglycemia. Subcutaneous or intramuscular injections of insulin results in peripheral hyperinsulinemia, resulting in the exacerbation of the macrovascular complications of diabetes (36,37). Due to these difficulties in achieving a normal physiological profile of insulin by injectable therapy, transmucosal delivery of insulin using gold nanoparticles offers a promising gateway.…”

Section: Resultsmentioning

confidence: 99%

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

et al. 2007

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Purpose. Colloidal metallic systems have been recently investigated in the area of nanomedicine. Gold nanoparticles have found themselves useful for diagnostic and drug delivery applications. Herein we have reported a novel method for synthesis of gold nanoparticles using a natural, biocompatible and biodegradable polymer; chitosan. Use of chitosan serves dual purpose by acting as a reducing agent in the synthesis of gold nanoparticles and also promotes the penetration and uptake of peptide hormone insulin across the mucosa. To demonstrate the use of chitosan reduced gold nanoparticles as carriers for drug delivery, we report herein the transmucosal delivery of insulin loaded gold nanoparticles. Materials and Methods. Gold nanoparticles were prepared using different concentrations of chitosan (from 0.01% w/v up to 1% w/v). The gold nanoparticles were characterized for surface plasmon band, zeta potential, surface morphology, in vitro diffusion studies and fluorescence spectroscopy. The in vivo studies in diabetic male Wistar rats were carried out using insulin loaded chitosan reduced gold nanoparticles.Results. Varying concentrations of chitosan used for the synthesis of gold nanoparticles demonstrated that the nanoparticles obtained at higher chitosan concentrations (>0.1% w/v) were stable showing no signs of aggregation. The nanoparticles also showed long term stability in terms of aggregation for about 6 months. Insulin loading of 53% was obtained and found to be stable after loading. Blood glucose lowering at the end of 2 h following administration of insulin loaded gold nanoparticles to diabetic rats was found to be 30.41 and 20.27% for oral (50 IU/kg) and nasal (10 IU/kg), respectively. Serum gold level studies have demonstrated significant improvement in the uptake of chitosan reduced gold nanoparticles. Conclusions. The synthesis of gold nanoparticles using a biocompatible polymer, chitosan would improve its surface properties for binding of biomolecules. Our studies indicate that oral and nasal administration of insulin loaded chitosan reduced gold nanoparticles has led to improved pharmacodynamic activity. Thus, chitosan reduced gold nanoparticles loaded with insulin prove to be promising in controlling the postprandial hyperglycemia.

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“…The wide range of CVs reported in different studies is probably due to the variety of methods used (radioactively labeled insulin [3,5], pharmacokinetic or pharmacodynamic measurements), differences regarding the number of replicate measurements (two to six [8,12,17,18]), and the injection site (thigh [13,18], upper arm [13], or abdomen [13]). The method to calculate variability also differs between studies.…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly true for basal insulin preparations. The few studies available report coefficients of variation (CVs) for within-and between-subject variability in the pharmacodynamic action of long-acting zinc insulin preparations to be between 35 and 55% (9) and even greater for NPH insulin (13). Compared with these findings, the variability (CV) of short-acting insulin preparations, which are reported in the range of "only" 20 -30% (10,11), are less of a concern.…”

mentioning

confidence: 99%

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

Heise

Nosek²,

Rønn³

et al. 2004

Diabetes

569

461

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The aim of this randomized double-blind study was to compare the within-subject variability of the glucoselowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 ؎ 10 years [ D aily clinical experience indicates that subcutaneous administration of insulin often does not result in a reproducible metabolic effect even when injected at the same dose under comparable conditions. Nonetheless, only few studies have assessed the variability of insulin absorption after subcutaneous administration (1-7), and even fewer have assessed the variability in the glucose-lowering effect of insulin. Thus, even though variability of the glucoselowering effect is regarded as a major obstacle to achieving optimal metabolic control (8 -10), our knowledge of the variability of insulin preparations is surprisingly scarce (11,12). This is particularly true for basal insulin preparations. The few studies available report coefficients of variation (CVs) for within-and between-subject variability in the pharmacodynamic action of long-acting zinc insulin preparations to be between 35 and 55% (9) and even greater for NPH insulin (13). Compared with these findings, the variability (CV) of short-acting insulin preparations, which are reported in the range of "only" 20 -30% (10,11), are less of a concern. The development of the new long-acting insulin analogs such as insulin detemir and insulin glargine has raised the hope of concurrent lower within-subject variability. However, insulin glargine does not appear to provide any improvement in the within-subject variability compared with NPH insulin (8).The aim of this study was to compare the within-subject variability in the glucose-lowering effect of the novel long-acting insulin analog insulin detemir with that of NPH insulin and insulin glargine. Insulin detemir [Lys B29 (N ε -tetradecanoyl) des(B30) human insulin] is the first of a new class of long-acting soluble insulin analogs. Its prolonged duration of action is attributable to a combination of increased self-association (hexamer stabilization and hexamer-hexamer interaction) and albumin binding due to acylation of the amino acid lysine in position B29 with a 14 C fatty acid (myristic acid). Insulin detemir is highly albumin bound in the interstitial fluid and in plasma (14) and has been shown to elicit a protracted metabolic action, with a slow onset of action and a less pronounced peak of action compared with that observed for NPH insulin (15,16).

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Factors Influencing the Absorption, Serum Insulin Concentration, and Blood Glucose Responses After Injections of Regular Insulin and Various Insulin Mixtures

Cited by 229 publications

References 0 publications

Glucose-lowering Effect of Insulin Degludec is Independent of Subcutaneous Injection Region

Glucose-lowering Effect of Insulin Degludec is Independent of Subcutaneous Injection Region

Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin

Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes

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