Blackshear Pj

TREATMENT OF A TYPE II DIABETIC BY A TOTALLY IMPLANTABLE INSULIN INFUSION DEVICE

Abstract The feasibility of treating type II diabetes by continuous intravenous infusion of insulin delivered by a totally implanted pump was tested in a 54-year-old man. An acceptable degree of blood glucose control was maintained while the patient carried on with his normal daily activities.

Glycerol Prevents Insulin Precipitation and Interruption of Flow in an Implantable Insulin Infusion Pump

Insulin precipitation is a major obstacle to the use of implantable insulin infusion pumps. In one such pump (Infusaid, Infusaid Corporation, Norwood, Massachusetts), unprotected insulin precipitated and occluded nine pumps implanted in normal dogs within 43 days. In contrast, two similar pumps containing insulin mixed with 80% glycerol functioned normally for more than 250 days. In human studies, a similar mixture allowed insulin to be delivered to nine diabetic subjects for more than 6 mo in each case; total fluid flow rates from the pump were essentially unchanged after 460 patients-weeks of insulin infusion. A possible drawback of the mixture is a time- and temperature-dependent propensity to cause the formation of soluble, higher-molecular-weight insulin polymers, which apparently have lower biologic activity. Formation of such polymers and maintenance of biologic activity were largely prevented by the addition of phosphate buffer at neutral pH.

Transbrachial hepatic arterial chemotherapy using an implanted infusion pump

Two patients with hepatic metastases from colonic cancer were treated with hepatic arterial FUDR using an innovative drug infusion system. The two patients reported underwent transbrachial hepatic artery catheterization with a 5 French polyethylene catheter. This catheter was amputated just distal to its exit from the brachial artery and attached to a totally implantable, percutaneously refillable drug infusion pump placed in the infraclavicular position. The patients received FUDR at flow rates of 3–4 ml/day. The pumps were refilled weekly by percutaneous injection. One patient was treated for seven weeks, and another for ten weeks without technical difficulties. This innovative approach offers marked improvement in comfort and convenience for patients who are candidates for long-term hepatic artery chemotherapy, and avoids the morbidity of laparotomy for direct hepatic arterial catheterization.

Protracted parenteral drug infusion in ambulatory subjects using an implantable infusion pump.

This study demonstrates the feasibility of ambulatory heparin therapy and its potential for successful treatment of refractory thromboembolic disease. The proven capability of the implantable infusion pump to provide long-term heparin infusion in ambulatory subjects suggests that it may have application in the delivery of other parenteral drugs as well.

Insulin binds to and promotes the phosphorylation of a Mr 210 000 component of its receptor in detergent extracts of rat liver microsomes

Insulin in the presence of Mn2+ and [γ32P]ATP promoted the phosphorylation of two proteins of M r 95 000 and M r 210 000 in detergent extracts of rat liver microsomes. The M r 210 000 protein was identified as a component of the insulin receptor by immunoprecipitation. It also bound [125I]insulin specifically, was phosphorylated largely on a tyrosine residue and could not be cleaved to smaller subunits under extreme reducing conditions. The M r 210 000 protein appears to be a component of a sub‐population of liver membrane insulin receptors in which insulin‐binding and insulin‐stimulated tyrosine kinase phosphorylation site(s) reside in a single polypeptide chain.

Protein Phosphorylations As a Mode of Insulin Action

Within minutes after the interaction of insulin with its receptor, marked changes occur in the metabolic pattern of the cell. In classic target tissues, insulin inhibits catabolic pathways (e.g., glycogenolysis and lipolysis), concurrently activating anabolic pathways (such as glycogen synthesis and de novo fatty acid synthesis). These effects are due to alterations in the activity of a variety of intracellular enzymes and transcellular transport processes. Over a longer period of time, insulin also participates in regulating the expression of specific genes and, in certain cell types, insulin modulates cell division and growth.

Basal-Rate Intravenous Insulin Infusion Compared to Conventional Insulin Treatment in Patients With Type II Diabetes: A Prospective Crossover Trial

We compared continuous basal-rate intravenous insulin infusion, delivered by means of a totally implantable pump, to two types of conventional insulin administration in patients with type II (non-insulindependent) diabetes in a prospective crossover trial. Ten patients entered the study, and 5 completed all three 8-mo study periods. When results from the infusion study period were compared with results from the periodinvolving single daily injections of ultralente insulin, significant improvements were noted in the pump arm in glycosylated hemoglobin concentrations (which were nearly normal), M-component values, mean daily outpatient fasting blood glucose concentrations, mean fasting and 24-h blood glucose concentrations during an inpatient 24-h glycemic profile, and urinary glucose concentrations. When the pump arm was compared to a period of single daily injections of lente insulin, three of six monthly mean fastingblood glucose concentrations and overall means for the entire study period were significantly lower during the pump arm than during the lente arm; in addition, significantly fewer hypoglycemic reactions were noted during infusion therapy than during lentetherapy. Finally, mealtime free-insulin and C-peptide excursions appeared to be greater during infusion treatment when compared with lente or ultralente treatment. In the 50% of patients who completed the study, it appeared that significant improvements in glycemic control could be achieved by simple basal-rate intravenous insulin infusion compared with conventional treatment with single daily injections of ultralente or lente insulin without an increased incidence of symptomatic hypoglycemia.