BACKGROUND Subcutaneously infused insulin may interfere with the function of nearby glucose-sensing electrodes and vice versa. The prototype of the Combo-Set device (Medtronic) incorporates a subcutaneous insulin delivery catheter and continuous glucose monitoring (CGM) sensor assembled on the same platform and separated by 11 mm. We aim to evaluate Combo-Set's insulin delivery and glucose-sens...

Insulin mucoadhesive buccal films (MBF) are a noninvasive insulin delivery system that offers an advantageous alternative route of administration to subcutaneous injection. One major concern in the formulation MBF is preservation secondary structure presence other film components. Buccal were formulated using chitosan, glycerin, and L-arginine. The MBF-forming solutions (MBF-FS) examined for th...

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling p...

In the normal state, pancreatic secretion of insulin results in a portallperipheral gradient with the highest concentrations of insulin in the liver. In diabetic patients with absent or insufficient pancreatic insulin secretion who require exogenous insulin, this normal gradient is lost, resulting in numerous abnormalities. This consideration led to interest in the intraperitoneal delivery of i...

As part of ongoing research into the use of vitamin B(12) (B(12); cobalamin; Cbl)-based bioconjugate approaches for the oral delivery of peptides/proteins, a molecular dynamics (MD) study of the binding of a cyanocobalamin-insulin (CN-Cbl-insulin) conjugate to human transcobalamin(II) (TCII) was recently reported that provides a qualitative picture of how the human insulin protein in its open "...

Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate four times of basal. In protocol 1, a full counterregulatory response was allowed...

Effective delivery of therapeutic biomolecules across biomembranes is a challenging topic. A cationic cyclopeptide named TD-34 (ACSSKKSKHCG) was reported to improve insulin delivery across biomembranes effectively. Based on our previous work, we investigated the mechanism of TD-34 for enhancing insulin across Caco-2 cell monolayers. Transport studies of insulin, TD-34 and insulin accompanied wi...

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in ...

OBJECTIVE This study evaluated the feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS In an open-label randomized crossover study, 12 suboptimally controlled adolescents on insulin pump therapy (mean ± SD age 14.6 ± 3.1 years; HbA1c 69 ± 8 mmol/mol [8.5 ± 0.7%]; du...

An automated closed-loop insulin delivery system based on subcutaneous glucose sensing and subcutaneous insulin delivery was evaluated in 10 subjects with type 1 diabetes (2 men, 8 women, mean [+/-SD] age 43.4 +/- 11.4 years, duration of diabetes 18.2 +/- 13.5 years). Closed-loop control was assessed over approximately 30 h and compared with open-loop control assessed over 3 days. Closed-loop i...