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OBJECTIVE-To describe the ability of nonhuman primate endocrine pancreata to reestablish endogenous insulin production after chemical β-cell destruction.
RESEARCH DESIGN AND METHODS-Eleven monkeys (Macaca fascicularis) were rendered diabetic with streptozotocin. Eight diabetic monkeys received intraportal porcine islet transplantation.
RESULTS-Two monkeys transplanted after 75 days of type 1 diabetes showed recovery of endogenous C-peptide production a few weeks after transplantation, concomitant with graft failure. Histological analysis of the pancreas of these monkeys showed insulin-positive cells, single or in small aggregates, scattered in the pancreas and adjacent to ducts. Interestingly, numerous CK19^sup +^ cells costained with proinsulin and PDX-1 antibodies. Furthermore, the peculiar double phenotype glucagon-positive/ GLUT2^sup +^ was observed. In these monkeys as well as in all others, the original islets showed no insulin staining.
CONCLUSIONS-Our data provide evidence that, in nonhuman primates, the pancreas can reestablish endogenous insulin production after chemical β-cell destruction. This seems to be a nongeneralizable event with only 2 out of 11 monkeys recovering β-cell function. In these two monkeys, younger age and islet graft behavior might have played a role in triggering endogenous β-cell recovery. Diabetes 58:442-447, 2009
Until a few years ago, lesions of the endocrine pancreas, as occur in type 1 diabetes, were thought to be permanent and irreversible, since diabetic patients require hormone replacement therapy for life (1). Despite the clinical evolution of the disease, it is still unknown whether the islet β-cells possess, at least in part, the ability to heal from an injury (2).
In mouse models, evidence has accrued that adult animals retain the ability to expand their β-cell mass after stimulation with a variety of triggers (3-8). It remains largely uncertain, however, through which molecular and cellular mechanisms the reparative process works (2).
In humans, the ability of the postnatal pancreas to expand the β-cell mass after injury is still debated (9,10). Spontaneous recovery of β-cell function has been reported in only few patients previously diagnosed with type 1 diabetes (11).
Although nonhuman primates do not develop autoimmune diabetes, a permanent diabetes status can be induced by total pancreatectomy or by chemical destruction of the β-cells with streptozotocin (STZ) (12,13).
In this study, a group of 11 monkeys were rendered diabetic by high STZ doses. Eight of them received intraportal pig islet...