Comparison of Subcutaneous Soluble Human Insulin and Insulin Analogues (AspB9, GluB27; AspB10; AspB28) on Meal-Related Plasma Glucose Excursions in Type I Diabetic Subjects

Kang, Seungha; Creagh, F. M.; Peters, John R.; Brange, Jens; Vølund, Aage; Owens, David R.

doi:10.2337/diacare.14.7.571

Cited by 88 publications

(43 citation statements)

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“…Subsequent studies confirmed that the rapid rate of absorption from the subcutaneous injection depot seen in pigs also occurred both in healthy volunteers and in patients with type 1 diabetes [14,15]. In a long-term double-blind, randomised crossover study with treatment periods of 2 months involving 21 male patients with type 1 diabetes, insulin X10 was shown to have a more physiological plasma profile than soluble human insulin [16].…”

Section: The Development Of Insulin X10mentioning

confidence: 56%

Insulin X10 revisited: a super-mitogenic insulin analogue

et al. 2011

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The molecular safety of insulin analogues has received a great deal of attention over the last year. In particular, attention has been directed to the mitogenic properties of insulin analogues as compared with human insulin. Understanding the mechanisms implicated in mediating mitogenic effects of insulin is therefore of particular interest. In this review we detail the story of the rapid-acting insulin analogue known as X10, which was the first insulin analogue in clinical development, but ended up being discontinued at an early clinical development stage following findings of mammary tumours in female Sprague-Dawley rats. The molecular characteristics of insulin X10, along with its interaction at both the IGF-1 receptor and the insulin receptor, have provided us with important insights into mechanisms implicated in metabolic and mitogenic signalling of insulin analogues.

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Section: The Development Of Insulin X10mentioning

confidence: 56%

Insulin X10 revisited: a super-mitogenic insulin analogue

et al. 2011

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“…Recent studies have revealed beneficial effects of acute and long-term (8 weeks) intranasal administration of regular human insulin (RH-I) on declarative memory in humans (Benedict et al, 2004;Reger et al, 2006). As RH-I molecules tend to self-associate into dimeric, tetrameric, and hexameric units, their absorption after subcutaneous administration is delayed (Kang et al, 1991). In the insulin analog insulin aspart (ASP-I), the amino-acid proline in position B28 is replaced by aspartic acid, reducing the tendency of the insulin molecule to self-associate (Brange et al, 1990;Brange and Volund, 1999), whereas the binding profile to the insulin receptor is the same as of RH-I (Kurtzhals et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

Benedict

Hallschmid

Schmitz

et al. 2006

Neuropsychopharmacol

264

157

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There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and longterm (4 Â 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (po0.01) and the RH-I groups (po0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (po0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.

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“…2). Relative to regular human insulin (100 ± 17 %) the plasma glucose area under the curve for the analogue was 51 ± 16 % (p < 0.02) [17]. Because of the more rapid decline in serum hormone concentrations one might also expect the risk of late hypoglycaemia to be reduced with the monomeric analogues.…”

Section: Fast-acting Monomeric Insulinsmentioning

confidence: 91%

“…Studies in insulin-dependent diabetic patients have demonstrated the beneficial pharmacokinetics and significant therapeutic value of monomeric insulin analogues [7,[16][17][18][19]. They yield a degree of glycaemic control, when injected just before a meal, at least comparable to that of human insulin administered 30 min before the meal [7,17]. Administration of insulin analogue Asp B28 resulted in a substantial reduction in the postprandial glucose excursion compared with that of human insulin injected 30 min earlier (Fig.…”

Section: Fast-acting Monomeric Insulinsmentioning

confidence: 99%

The new era of biotech insulin analogues

Brange

1997

Diabetologia

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The introduction of insulin in the 1920 s revolutionized the treatment of diabetes mellitus. However, pancreatic insulin did not evolve for exogenous administration, and subcutaneous injection therapy has not succeeded in normalizing glycaemic control despite the great efforts devoted to improvements in insulin preparations and injection regimens. The increasing awareness and acceptance of the relationship between metabolic control and the occurrence of devastating microvascular complications have stimulated considerable research into new methods of improving insulin therapy.In the field of pharmaceutical formulation important improvements have emerged. However, the pharmacokinetics following subcutaneous injection of the currently available rapid-, intermediate-and long-acting insulin preparations make it virtually impossible to achieve normoglycaemia. The absorption of insulin from the injection site is a complex process affected by many factors, such as location of the site, physical state of the patient and the nature of the insulin preparation. After subcutaneous injection of regular insulin into the femoral region it takes 2-4 h for the insulin to be absorbed at maximum rate. This slow rise to peak insulin concentration is likely to account for much of the observed postprandial hyperglycaemia seen in diabetic subjects. As the insulin concentration falls slowly after the peak, the extended period of elevated insulin concentration results in a tendency towards late hypoglycaemia. Such plasma insulin patterns bear no resemblance to those in normal subjects in response to a meal. After subcutaneous injection of soluble insulin an initial phase (lag phase) with low but increasing relative rate of absorption has been observed in most clinical studies. This initial delay in absorption is shortened or even disappears when reducing the concentration of insulin or decreasing the volume injected [1].Until recently advances in insulin formulation were limited to improvements in insulin purity, insulin Diabetologia (1997) 40: S 48-S 53 The new era of biotech insulin analogues J. BrangeNovo Nordisk A/S, Bagsvaerd, Denmark © Springer-Verlag 1997Corresponding author: Dr. J. Brange, Novo Nordisk A/S, Building 6A, Novo Alle, DK-2880 Bagsvaerd, Denmark Summary Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for the biological action of the hormone. It is therefore not surprising that wild-type insulin has far from optimal characteristics for replacement therapy. For example, native human insulin self-associates to hexameric units, which limits the possibilities for the absorption of the molecule by various routes. During the last decade new techniques of molecular design have emerged and recombinant DNA technology offers new and exciting opportunities for rational protein drug design. This review describes examples of recent advances in insulin engineering aimed at op...

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Comparison of Subcutaneous Soluble Human Insulin and Insulin Analogues (AspB9, GluB27; AspB10; AspB28) on Meal-Related Plasma Glucose Excursions in Type I Diabetic Subjects

Cited by 88 publications

References 0 publications

Insulin X10 revisited: a super-mitogenic insulin analogue

Insulin X10 revisited: a super-mitogenic insulin analogue

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

The new era of biotech insulin analogues

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