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Biomedical subjects

Richard Olsson

Publications and source records attributed to Richard Olsson.

10 recordsLinked to original sources
PubMed2006

Revascularization of transplanted pancreatic islets following culture with stimulators of angiogenesis.

BACKGROUND: Insufficient revascularization of transplanted islets may result in chronic hypoxia and loss of islet function. This study investigated whether simple culture of islets with angiogenic substances before transplantation could improve graft revascularization. METHODS: Mouse islets were cultured with vascular endothelial growth factor (VEGF; 20 ng/ml), fibroblast growth factor 2 (FGF-2; 20 ng/ml) or matrix metalloproteinase 9 (MMP-9; 1 mug/ml). Thereafter, 250 islets were implanted beneath the renal capsule of syngeneic C57Bl/6 mice. One month posttransplantation, blood flow (laser-Doppler flowmetry), oxygen tension (Clark microelectrodes), and vascular density were measured and correlated to graft function. RESULTS: Treatment of islets with VEGF during culture caused islet blood vessels to dilate, whereas FGF-2 treatment induced endothelial cell proliferation. However, the number of capillaries in both cases decreased during culture. When investigated one month posttransplantation, both VEGF and FGF-2 pretreated islets had similar or worse vascular engraftment when compared to transplanted control islets. MMP-9 pretreatment of islets increased vascular density, blood flow and oxygen tension within the grafts. Animals receiving MMP-9 pretreated islets returned, however, more slowly to normoglycemia than control animals, and performed worse than controls in a glucose tolerance test one month posttransplantation. CONCLUSIONS: Treatment of islets during culture with VEGF or FGF-2 changed the islet vascular phenotype, but capillaries were still lost. Notably, the number of capillaries in the grafted islets one month posttransplantation was in all cases strikingly similar to that observed prior to transplantation. MMP-9 pretreatment of islets elicited an angiogenic response, which improved revascularization of the transplanted islets.

Angiogenesis Inducing Agents↗
PubMed2006

The pancreatic islet endothelial cell: emerging roles in islet function and disease.

The pancreatic islets are one of the most vascularized organs of the body. This likely reflects the requirements of the organ for a rich supply of nutrients and oxygen to the tissue, as well as the need for rapid disposal of metabolites and secreted hormones. The islet endothelium is richly fenestrated to facilitate trans-endothelial transport of secreted hormones, has a unique expression of surface markers, and produces a number of vasoactive substances and growth factors. The islet endothelial cells play a critical role in the early phase of type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing receptors, thereby enabling immune cells to enter the endocrine tissue and cause beta-cell destruction. Following transplantation, pancreatic islets lack a functional capillary system and need to be properly revascularized. Insufficient revascularization may severely affect the transport properties of the islet endothelial system, resulting in a dysfunctional islet graft.

Journal Article↗
PubMed2005

The pancreatic islet endothelial cell: emerging roles in islet function and disease.

The pancreatic islets are one of the most vascularized organs of the body. This likely reflects the requirements of the organ for a rich supply of nutrients and oxygen to the tissue, as well as the need for rapid disposal of metabolites and secreted hormones. The islet endothelium is richly fenestrated to facilitate trans-endothelial transport of secreted hormones, has a unique expression of surface markers, and produces a number of vasoactive substances and growth factors. The islet endothelial cells play a critical role in the early phase of type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing receptors, thereby enabling immune cells to enter the endocrine tissue and cause beta-cell destruction. Following transplantation, pancreatic islets lack a functional capillary system and need to be properly revascularized. Insufficient revascularization may severely affect the transport properties of the islet endothelial system, resulting in a dysfunctional islet graft.

Animals↗
PubMed2004

Expression and distribution of somatostatin receptor subtypes in the pancreatic islets of mice and rats.

Somatostatin acts on specific membrane receptors (sst(1-5)) to inhibit exocrine and endocrine functions. The aim was to investigate the distribution of sst(1-5) in pancreatic islet cells in normal mice and rats. Pancreatic samples from five adult C57BL/6 mice and Sprague-Dawley rats were stained with antibodies against sst(1-5) and insulin, glucagon, somatostatin, or pancreatic polypeptide (PP). A quantitative analysis of the co-localization was performed. All ssts were expressed in the pancreatic islets and co-localized on islet cells to various extents. A majority of the beta-cells expressed sst(1-2) and sst(5) in mouse islets, while < or =50% in the rat expressed sst(1-5). The expression of sst(1-5) on alpha-cells did not differ much among species, with sst(2) and sst(5) being highly expressed. About 70% of the delta-cells expressed sst(1-4) in the rat pancreas, whereas 50% of the islet cells expressed sst(1-5) in the mouse. Furthermore, 60% of the PP-cells expressed sst(1-5) in the mouse, while the rat islets had lower values. Co-expression with the four major islet hormones varies among species and sst subtypes. These similarities and differences are interesting and need further evaluation to elucidate their physiological role in islets.

Animals↗
PubMed2004

Promoting islet cell function after transplantation.

Engraftment (i.e., the adaptation of transplanted pancreatic islets to their new surroundings with regard to revascularization, reinnervation, and reorganization of other stromal compartments) is of crucial importance for the survival and function of the endocrine cells. Previous studies suggest that transplantation induces both vascular and stromal dysfunctions in the implanted islets when compared with endogenous islets. Thus the vascular density and the blood perfusion of islet grafts is decreased and accompanied with a capillary hypertension. This leads to hypoxic conditions, with an associated shift toward anaerobic metabolism in grafted islets. An improved engraftment will prevent or compensate for the vascular/stromal dysfunction seen in transplanted islets and thereby augment survival of the islet implant. By such means the number of islets needed to cure the recipient will be lessened. This will increase the number of patients that can be transplanted with the limited material available.

Animals↗
PubMed2003

[Severe vascular dysfunction shown in transplanted islets].

Despite recent advances in clinical islet transplantation, a surprisingly large number of islets (approximately 1 million) are still required to obtain insulin independence in type 1 diabetes. The reasons for this are obscure and likely multifactorial. One explanation may be disturbances in engraftment of the transplanted islets, i.e. the adaptation of the islet transplant to its new surroundings with regard to e.g. revascularization and blood perfusion. Endogenous islets have a dense glomerular-like angioarchitecture. Transplantation of isolated islets causes a disruption of their vascular connections, making the islets dependent on the formation of new blood vessels for optimal function. Evidence from experimental islet transplantation indicates an insufficient revascularization of transplanted islets with subsequent chronically decreased blood perfusion and oxygen tension, which has metabolic consequences within the tissue.

Animals↗
PubMed2002

Prostaglandin E2 induces vasodilation and pruritus, but no protein extravasation in atopic dermatitis and controls.

BACKGROUND: Prostaglandin E(2) (PGE(2)) has well-established vasodilatory effects, whereas its effects on protein extravasation and its sensory effects are less clear. OBJECTIVE: Vasoactive effects of PGE(2) were correlated to its ability to evoke pain or itch in healthy volunteers and patients with atopic dermatitis (AD). METHODS: Intradermal microdialysis was used to apply PGE(2) (10(-8)-10(-4) M) via microdialysis capillaries in 8 patients and 8 controls. Large pore size membranes (3000 kd) enabled simultaneous analysis of protein extravasation. Itch and pain sensations were measured psychophysically, and superficial blood flow was measured by laser Doppler imaging. RESULTS: PGE(2) dose dependently provoked intense local vasodilation, weak pruritus, and pain, but no protein extravasation. No differences were found between patients with AD and controls for any parameter. CONCLUSION: We conclude that PGE(2) is a potent vasodilator and a weak pruritic agent in normal skin and in patients with AD, but does not provoke increased protein extravasation.

Adult↗
PubMed2002

Microdialysis measurements demonstrate a shift to nonoxidative glucose metabolism in rat pancreatic islets transplanted beneath the renal capsule.

BACKGROUND: We aimed to use microdialysis to assess, for the first time, the internal milieu of pancreatic islet grafts. METHODS: One month after transplantation, microdialysis probes were inserted into syngeneic rat islet transplants (500-700 islets) placed beneath the renal capsule of nondiabetic or diabetic recipients. The number of grafted islets was purposely chosen not to cure the diabetic recipients. RESULTS: During an intravenous glucose challenge, insulin concentrations increased in parallel in serum and in the graft interstitium of nondiabetic animals suggesting the existence of a functionally well-established vascularization. Diabetic recipients had both a lower serum and dialysate insulin concentration than normoglycemic animals. The lactate/pyruvate ratios were determined in the dialysates as a measure of the degree of anaerobic metabolism in the islet grafts. Lactate/pyruvate ratios were between 50 and 100 in grafts of both nondiabetic and diabetic recipients, and they almost doubled in response to the intravenous glucose challenge in the grafts of nondiabetic recipients. In comparison, lactate/pyruvate ratios were approximately 12 in the medium of cultured islets incubated at low glucose (5.6 mmol/L) or high glucose (16.7 mmol/L) concentrations. CONCLUSIONS: The microdialysis technique has proven to be a valuable tool for evaluating the internal environment of islet transplants. Moreover, the high lactate/pyruvate ratio suggests that islet grafts have an increased anaerobic glucose metabolism.

Animals↗
PubMed2002

Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators.

This study investigated the mechanisms for glucose-induced islet blood flow increase in rats. The effects of adenosine, adenosine receptor antagonists, and vagotomy on islet blood flow were evaluated with a microsphere technique. Vagotomy prevented the islet blood flow increase expected 3, 10, and 20 min after injection of glucose, whereas theophylline (a nonspecific adenosine receptor antagonist) prevented the islet blood flow increase from occurring 10 and 20 min after glucose administration. Administration of selective adenosine receptor antagonists suggested that the response to theophylline was mediated by A1 receptors. Exogenous administration of adenosine did not affect islet blood flow, but local accumulation of adenosine, induced by the adenosine uptake inhibitor dipyridamole, caused a doubling of islet blood flow. In conclusion, the increased islet blood flow seen 3 min after induction of hyperglycemia is caused by the vagal nerve, whereas the increase in islet blood perfusion seen at 10 and 20 min after glucose administration is caused by both the vagal nerve and adenosine.

Adenosine↗