Regression of diabetic complications by islet transplantation in the rat

Abstract

Aims/hypothesis Type 1 diabetes is a chronic disease leading to complications such as peripheral neuropathies, nephropathy and cardiovascular disease. Pancreatic islet transplantation is being extensively investigated for blood glucose control in animals and in human type 1 diabetic patients, but the question of whether it can reverse long-term diabetic complications has not been fully explored. We investigated the effects of islet transplantation on diabetic complications in a rat model of streptozotocin-induced diabetes.Methods Three groups of rats were used: healthy controls, diabetic and diabetic rats transplanted with microencapsulated islets at 2 months after diabetes induction, when neuropathy was detectable by a decrease in tail nerve conduction velocity (NCV) and impaired nociceptive thresholds. Blood glucose levels and body weight were measured weekly. The variables considered were: thermal (hot plate test) and mechanical sensitivity (Randal-Selitto paw withdrawal test), NCV and Na+, K+-ATPase activity in the sciatic nerve. At the end of the experiments hearts were removed for morphometric determination and myocyte number, and kidneys removed for histological examination. Results Islet transplantation in diabetic rats induced normoglycaemia in a few days, accompanied by a rapid rise in body weight and amelioration of impaired nociceptive thresholds, as well as normalisation of NCV and Na + , K + -ATPase, which were both about 25% below normal in diabetic rats. Myocyte loss was reduced (−34%) by islet transplantation and the observed mild kidney damage of diabetic rats was prevented. Conclusions/interpretation Besides controlling glycaemia, transplantation of microencapsulated pancreatic islets induced almost complete regression of neuropathy and prevented cardiovascular alterations.

C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia

“…Animal studies and clinical phase I/II trials in patients with T1D who take C-peptide as replacement therapy provide direct evidence of a protective effect of C-peptide against diabetes-induced complications of the kidneys, the peripheral nerves, and CNS function [18][19][20]. In addition, it has been shown that T1D patients with residual beta cell function or receiving whole pancreas or allogeneic islet transplantation do not develop long-term complications, a result that could be attributed to a positive effect of C-peptide [21][22][23][24][25]. These results identify C-peptide as a compelling novel therapeutic candidate in T1D.…”

Islet transplantation in rodents: do encapsulated islets really work?

“…Figliuzzi et al (11) 16000 IS+: 18 ± 8 IS-: 7.5 ± 0.2 Yun Lee et al (63) 1200 >365 Remuzzi A et al (39) 3000 80 O'Sullivan et al (36) …”

Evaluation of left and right ventricular functions using conventional and tissue Doppler echocardiography in children with type 1 diabetes mellitus

“…Various independent investigators have shown that in diabetic patients there is extensive impairment in left ventricular functions before the clinical signs of congestive heart failure become manifest. Diastolic dysfunction has been defined as the earliest sign of diabetic myocardial disease to occur before systolic impairment [2,12,13].…”

“…The term diabetic cardiomyopathy (DCM) refers to heart disease caused by diabetes. DM is asymptomatic in the early stages and it is associated with a poor prognosis and irreversible changes [2]. Although there are many studies conducted in adult patients, there are a very limited number of studies in children and adolescents in the literature.…”