scholarly journals Ultra‐Fast Insulin–Pramlintide Co‐Formulation for Improved Glucose Management in Diabetic Rats

2021 ◽  
pp. 2101575
Author(s):  
Caitlin L. Maikawa ◽  
Peyton C. Chen ◽  
Eric T. Vuong ◽  
Leslee T. Nguyen ◽  
Joseph L. Mann ◽  
...  
2021 ◽  
Author(s):  
Caitlin L Maikawa ◽  
Peyton C Chen ◽  
Eric T Vuong ◽  
Leslee T Nguyen ◽  
Joseph L Mann ◽  
...  

Dual-hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co-secretion. Here, we use amphiphilic acrylamide copolymers to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action. The co-formulation is stable for over 16 hours under stressed aging conditions that cause a commercial "fast-acting" insulin formulation, Humalog, to aggregate in only 8 hours. The faster insulin pharmacokinetics achieved by delivery of monomeric insulin alongside pramlintide in this new co-formulation resulted in an increased overlap of 75 (s.e. = 6)% compared to only 47 (s.e. = 7)% for separate injections. Pramlintide delivered in the co-formulation resulted in similar delay in gastric emptying compared to pramlintide delivered separately, indicating pramlintide efficacy is maintained in the co-formulation. In a glucose challenge, rats receiving the co-formulation had reduced deviation from baseline glucose compared to treatment with either Humalog alone or separate injections of Humalog and pramlintide. Together these results suggest that a stable co-formulation of monomeric insulin and pramlintide has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.


Author(s):  
Burton B. Silver ◽  
Ronald S. Nelson

Some investigators feel that insulin does not enter cells but exerts its influence in some manner on the cell surface. Ferritin labeling of insulin and insulin antibody was used to determine if binding sites of insulin to specific target organs could be seen with electron microscopy.Alloxanized rats were considered diabetic if blood sugar levels were in excess of 300 mg %. Test reagents included ferritin, ferritin labeled insulin, and ferritin labeled insulin antibody. Target organs examined were were diaphragm, kidney, gastrocnemius, fat pad, liver and anterior pituitary. Reagents were administered through the left common carotid. Survival time was at least one hour in test animals. Tissue incubation studies were also done in normal as well as diabetic rats. Specimens were fixed in gluteraldehyde and osmium followed by staining with lead and uranium salts. Some tissues were not stained.


2001 ◽  
Vol 120 (5) ◽  
pp. A674-A674 ◽  
Author(s):  
A FUNAKOSHI ◽  
M ICHIKAWA ◽  
Y SATO ◽  
S KANAI ◽  
M OHTA ◽  
...  

2007 ◽  
Vol 177 (4S) ◽  
pp. 264-265
Author(s):  
Ling De Young ◽  
KokBin Lim ◽  
Jeffery Carson ◽  
Trustin Domes ◽  
Mussa Al-Numi ◽  
...  

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
DK Rai ◽  
PK Rai ◽  
B Sharma ◽  
G Watal

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