ArticleDiabetes2015
Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus.Clinical pharmacology in drug development · 2020Trial
- Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with insulin glargine: pooled analyses of five randomized controlled trials.Diabetes, obesity & metabolism · 2016Trial
- A one-week reduced-carbohydrate diet lowers insulin requirements and shifts the IGF axis with no detectable short-term change in endothelial function in a randomized, crossover trial of adults with type 1 diabetes.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Skeletal muscle mitochondrial health in type 1 diabetes: the role of exercise capacity and lifestyle factors.Diabetologia · 2025Article
- The Effects of Resistance Exercise Training on Skeletal Muscle Metabolism and Insulin Resistance Development in Female Rodents with Type 1 Diabetes.Journal of diabetes research · 2024Article
- Delivery of biologics: Topical administration.Biomaterials · 2023Review
- Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin.Biomaterials · 2023Article
- Article
- Autoimmune Inflammation and Insulin Resistance: Hallmarks So Far and Yet So Close to Explain Diabetes Endotypes.Current diabetes reports · 2021Review
- Importance of the route of insulin delivery to its control of glucose metabolism.American journal of physiology. Endocrinology and metabolism · 2021Article
- The Peripheral Peril: Injected Insulin Induces Insulin Insensitivity in Type 1 Diabetes.Diabetes · 2020Review
- Peripherally delivered hepatopreferential insulin analog insulin-406 mimics the hypoglycaemia-sparing effect of portal vein human insulin infusion in dogs.Diabetes, obesity & metabolism · 2019Article
- Article
- A New Animal Model of Insulin-Glucose Dynamics in the Intraperitoneal Space Enhances Closed-Loop Control Performance.Journal of process control · 2019Article
- Targeting insulin to the liver corrects defects in glucose metabolism caused by peripheral insulin delivery.JCI insight · 2019Article
- Article
- Enterically delivered insulin tregopil exhibits rapid absorption characteristics and a pharmacodynamic effect similar to human insulin in conscious dogs.Diabetes, obesity & metabolism · 2019Article
- Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes.Diabetologia · 2018Article
- Finding the right route for insulin delivery - an overview of implantable pump therapy.Expert opinion on drug delivery · 2017Review
- Glucose autoregulation is the dominant component of the hormone-independent counterregulatory response to hypoglycemia in the conscious dog.American journal of physiology. Endocrinology and metabolism · 2017Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
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, whereas in protocol 2, glucagon was fixed at basal, mimicking the diminished α-cell response to hypoglycemia seen in T1DM. In protocol 1, glucose fell faster with Pe insulin than with Po insulin, reaching 56 ± 3 vs. 70 ± 6 mg/dL (P = 0.04) at 60 min. The change in area under the curve (ΔAUC) for glucagon was similar between Pe and Po, but the peak occurred earlier in Pe. The ΔAUC for epinephrine was greater with Pe than with Po (67 ± 17 vs. 36 ± 14 ng/mL/180 min). In protocol 2, glucose also fell more rapidly than in protocol 1 and fell faster in Pe than in Po, reaching 41 ± 3 vs. 67 ± 2 mg/dL (P < 0.01) by 60 min. Without a rise in glucagon, the epinephrine responses were much larger (ΔAUC of 204 ± 22 for Pe vs. 96 ± 29 ng/mL/180 min for Po). In summary, Pe insulin delivery exacerbates hypoglycemia, particularly in the presence of a diminished glucagon response. Po vein insulin delivery, or strategies that mimic it (i.e., liver-preferential insulin analogs), should therefore lessen hypoglycemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.