title: Closed-loop glycaemic control using an implantable artificial pancreas in diabetic domestic pig (Sus scrofa domesticus).
abstract: The performance of a completely implantable peritoneal artificial pancreas (AP) has been demonstrated in principle in a live diabetic domestic pig. The device consists of a smart glucose-sensitive gel that forms a gateway to an insulin reservoir and is designed to both sense glucose and deliver insulin in the peritoneal cavity. It can be refilled with insulin via subcutaneous ports and surgery was developed to insert the AP. Diabetes was induced with streptozotocin (STZ), the device filled with insulin (Humulin(®) R U-500) in situ and the animal observed for several weeks, during which time there was normal access to food and water and several oral glucose challenges. Blood glucose (BG) levels were brought down from >30 mmol/L (540 mg/dL) to non-fasted values between 7 and 13 mmol/L (126-234 mg/dL) about five days after filling the device. Glucose challenge responses improved ultimately so that, starting at 10 mmol/L (180 mg/dL), the BG peak was 18 mmol/L (324 mg/dL) and fell to 7 mmol/L (126 mg/dL) after 30 min, contrasting with intravenous attempts. The reservoir solution was removed after 8 days of blood glucose levels during which they had been increasingly better controlled. A rapid return to diabetic BG levels (30 mmol/L) occurred only after a further 24 days implying some insulin had remained in the device after removal of the reservoir solution. Thus, the closed loop system appeared to have particular influence on the basal and bolus needs for the 8 days in which the reservoir solution was in place and substantial impact for a further 3 weeks. No additional insulin manual adjustment was given during this period.
authors.affiliation: Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom. Electronic address: mjt@dmu.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Taylor
authors.affiliation: Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Gregory
authors.affiliation: Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Tomlins
authors.affiliation: Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Jacob
authors.affiliation: Department of Chemical Engineering, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Hubble
authors.affiliation: Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom.
authors.forename: T S
authors.initials: TS
authors.lastname: Sahota
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D019397:Pancreas, Artificial; D034421:Sus scrofa
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Artificial pancreas; Closed-loop; Diabetes; Glucose-sensitive; Implantable; Insulin; Smart material