Advances in insulin therapy from discovery to β‐cell replacement

Abstract

Insulin therapy using insulin purified from porcine or bovine pancreas revolutionized diabetes therapy in the 1920s. A series of advances including cloning human insulin cDNA enabled the development of recombinant human insulin with improved features. Insulin treatment for diabetes may well be upended by β‐cell replacement therapy in the coming decades.

Noninvasive quantitative evaluation of viable islet grafts using 111In‐exendin‐4 SPECT/CT

“…Direct assessments of islet graft BCM remain challenging in current clinical evaluations of transplantation efficacies 12,13 . Recently, the development of exendin‐based GLP‐1R‐targeted β‐cell imaging has shed light on this issue 4,13,14 . However, most studies involving such imaging have focused on insulinoma or the pancreas alone, 16,24,27–29 whereas only a limited number of studies have examined the possibility of islet graft evaluation for IT.…”

“…12,13 Recently, the development of exendinbased GLP-1R-targeted βcell imaging has shed light on this issue. 4,13,14 However, most studies involving such imaging have focused on insulinoma or the pancreas alone, 16,24,[27][28][29] whereas only a limited number of studies have examined the possibility of islet graft evaluation for IT. Eter et al reported that 111 In-exendin-3 SPECT/CT displayed islet grafts in intramuscular IT mice, and the uptake in calf muscle correlated with graft volume 30,31 ; however, muscle is not favorable in IT and intramuscular transplantation remains very uncommon in the clinic.…”

“…2 βcell replacement therapy, such as pancreatic islet transplantation (IT) via the portal vein, represents a promising method for achieving BCM restoration and glycemic stability with or without a reduced insulin requirement. 3,4 Although the current method has yielded favorable outcomes for IT, only 32% and 8% of patients remained insulin independent 5 and 20 years later, respectively. 5,6 In addition, repeated ITs are required to maintain a certain level of BCM for maintaining an insulin-independent status.…”

“…In type 1 diabetes, a substantial β‐cell loss is observed because of autoimmune destruction, which results in a constant need for insulin replacement therapy 2 . β‐cell replacement therapy, such as pancreatic islet transplantation (IT) via the portal vein, represents a promising method for achieving BCM restoration and glycemic stability with or without a reduced insulin requirement 3,4 . Although the current method has yielded favorable outcomes for IT, only 32% and 8% of patients remained insulin independent 5 and 20 years later, respectively 5,6 .…”

An update of contemporary insulin therapy

“…A century has elapsed since the first formulated insulin made a debut. Progressive techniques and materials have overcome many problems of insulin therapy, including impurities, duration of action, antibodies against porcine or bovine insulin, and the expense of production 1 .…”