Absorption of Insulin from the Human Small Intestine

Crane, Chilton; Luntz, G. R. W. N.

doi:10.2337/diab.17.10.625

Cited by 56 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies of the effects of insulin administered orally may not have been undertaken previously because insulin administered in this manner is assumed to be degraded rapidly (27). Neverthe- less, pharmacologic doses of oral insulin (more than 170-fold higher than those used in our study) administered to piglets and human infants less than 24-h-old decreased serum glucose, presumably by having been absorbed (28,29).…”

Section: Discussionmentioning

confidence: 87%

Oral Insulin Increases Small Intestinal Mass and Disaccharidase Activity in the Newborn Miniature Pig

Shulman

1990

Pediatric Research

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 87%

Oral Insulin Increases Small Intestinal Mass and Disaccharidase Activity in the Newborn Miniature Pig

Shulman

1990

Pediatric Research

View full text Add to dashboard Cite

“…These factors may explain why ϳ0.5% of an oral insulin dose may reach the systemic circulation (22). Because of these obstacles, it would be extremely difficult to consider oral insulin therapy as a physiological option for premeal dosing (6).…”

Section: Oral Entericmentioning

confidence: 99%

Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery

Cefalu

2004

Diabetes Care

147

View full text Add to dashboard Cite

OBJECTIVE -To comprehensively review the progress to date on the development of alternative routes for insulin delivery. RESEARCH DESIGN AND METHODS -Study data were collected through a Medline review.RESULTS -Proof of principle has been established for many routes of administration including dermal, nasal, oral, buccal, and pulmonary insulin delivery.CONCLUSIONS -Of all the approaches to date, pulmonary delivery appears to be most feasible. Ongoing phase III studies will ultimately determine safety, tolerability, and efficacy before approval for clinical use. Diabetes Care 27:239 -246, 2004T he therapeutic insulin era began on 11 January 1922 with the first clinical use of insulin by Banting and Best. In Ͻ2 years, insulin moved "from the realm of hypothesis to the reality of treatment" (1). In the ensuing 80 years, scientists uncovered the basic pathophysiology of diabetes, gradually elucidated insulin's structure, and focused their attention on developing better insulin formulations (e.g., NPH, lente). In this regard, the development and availability of rapid-acting (e.g., lispro, aspart) and basal insulins (e.g., glargine) have allowed for the routine use of very physiological insulin regimens.However, despite significant research, the first effective noninvasive delivery systems for insulin are only now in development, marking a new milestone in effective management of diabetes. There is a clinical need for such because insulin therapy is central to the treatment of people with type 1 diabetes. Intensive insulin therapy, in particular, is associated with better long-term clinical outcomes. The progressive decrease in ␤-cell function evident in the pathogenesis of type 2 diabetes means that the majority of patients will eventually fail on oral therapy and will require insulin therapy at some point. Furthermore, oral agent failure is just one of a number of situations where insulin therapy might be indicated in patients with type 2 diabetes (2).Despite the benefits of tight glycemic control, which ultimately can only be achieved with insulin in type 2 diabetic patients, there is reluctance on the part of physicians and patients to initiate insulin therapy (2). Factors such as weight gain, social stigma, lifestyle restriction, injection anxiety, sense of guilt or failure, and perception of worsening disease may affect patients' attitudes. Although hypoglycemia and weight gain are also perceived as barriers, these factors should not discourage the start of insulin. This reluctance contributes to poor glycemic control, and any advances that can help to minimize such concerns clearly have a place in diabetes management.NONINVASIVE INSULIN DELIVERY -Originally, insulin was administered intramuscularly. It soon became clear that subcutaneous injections were just as effective but considerably less traumatic (3). Over the years, researchers have suggested transdermal, ocular, oral, buccal, nasal, rectal, vaginal, and uterine delivery systems (3,4). However, subcutaneous administration has remained the route of choice,...

show abstract

“…Unfortunately, insulin is less absorbed by the intestinal mucosa since no more than 0.5% is absorbed under the best experimental conditions. 21 In addition, insulin is degraded in the gastrointestinal tract by proteolytic enzymes. Thus, to overcome these major problems, it was suggested to associate insulin to absorption enhancers and enzyme proteases.…”

Section: Introductionmentioning

confidence: 99%

Poly(alkyl cyanoacrylate) Nanospheres for Oral Administration of Insulin

Damgé¹,

Vranckx

Balschmidt

et al. 1997

Journal of Pharmaceutical Sciences

150

View full text Add to dashboard Cite

Poly(alkyl cyanoacrylate) nanocapsules have been successfully used for oral administration of insulin in diabetic rats. This work reports a suitable formulation for insulin-loaded nanospheres composed of full polymeric structures formed by polymerization of isobutyl cyanoacrylate (IBCA) in an acidic medium, insulin (15 U/mL) being added to the polymerization medium 60 min after the onset of polymerization. These nanospheres (MW 364) displayed a mean size of 145 nm and an association rate of 1 U of insulin/mg of polymer. They protected insulin from the degradation by proteolytic enzymes in vitro, especially when they were dispersed in an oily medium (Miglyol 812) containing surfactive agents (Poloxamer 188 and deoxycholic acid). When dispersed in the same medium, insulin-loaded nanospheres (100 U/kg of body weight), administered perorally in streptozotocin-induced diabetic rats, provoked a 50% decrease of fasted glycemia from the second hour up to 10-13 days. This effect was shorter (2 days) or absent when nanospheres were dispersed in water with surfactive agents or not. Using 14C-labeled nanospheres loaded with [125I]insulin, it was found that nanospheres increased the uptake of [125I]insulin or its metabolites in the gastrointestinal tract, blood, and liver while the excretion was delayed when compared to [125I]insulin nonassociated to nanospheres; in addition, 14C- and 125I-radioactivities disappeared progressively as a function of time, parallel to the biological effect. Thus insulin-loaded nanospheres can be considered as a convenient delivery system for oral insulin at the prerequisite that they were dispersed in an oily phase containing surfactants.

show abstract

Absorption of Insulin from the Human Small Intestine

Cited by 56 publications

References 0 publications

Oral Insulin Increases Small Intestinal Mass and Disaccharidase Activity in the Newborn Miniature Pig

Oral Insulin Increases Small Intestinal Mass and Disaccharidase Activity in the Newborn Miniature Pig

Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery

Poly(alkyl cyanoacrylate) Nanospheres for Oral Administration of Insulin

Contact Info

Product

Resources

About