Biomedical subjects

Darin E Olson

Publications and source records attributed to Darin E Olson.

6 recordsLinked to original sources

PubMed2006

Structural and functional MRI reveals multiple retinal layers.

MRI is a noninvasive diagnostic modality that reveals anatomy, physiology, and function in vivo without depth limitation or optical interference. MRI application to the retina, however, remains challenging. We improved spatial resolution to resolve layer-specific structure and functional responses in the retina and confirmed the laminar resolution in an established animal model of retinal degeneration. Structural MRI of normal rat retinas revealed three bands corresponding histologically to (i) the combined ganglion cell layer/inner nuclear layer plus the embedded retinal vessels, (ii) the avascular outer nuclear (photoreceptor) layer and its photoreceptor segments, and (iii) the choroidal vascular layer. Imaging with an intravascular contrast agent (gadolinium-diethylene-tri-amine-pentaacetic acid) enhanced the retinal and choroidal vascular layers bounding the retina, but not the avascular outer nuclear layer and the vitreous. Similarly, blood-oxygen-level-dependent (BOLD) functional MRI revealed layer-specific responses to hyperoxia and hypercapnia. Importantly, layer-specific BOLD responses in the two vascular layers were divergent, suggesting the two vasculatures are differentially regulated. To corroborate sensitivity and specificity, we applied layer-specific MRI to document photoreceptor degeneration in Royal College of Surgeons rats. Consistent with histology, layer-specific MRI detected degeneration of the outer nuclear layer. Surprisingly, MRI revealed increased thickness in the choroidal vascular layer and diminished BOLD responses to hyperoxia and hypercapnia in the Royal College of Surgeons rat retinas, suggesting perturbation of vascular reactivity secondary to photoreceptor loss. We conclude that MRI is a powerful investigative tool capable of resolving lamina-specific structures and functional responses in the retina as well as probing lamina-specific changes in retinal diseases.

Aging↗

PubMed2005

Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in diabetic rodents, suggesting that similar approaches may eventually provide a means to improve treatment of diabetes mellitus. However, whether the metabolic and hormonal changes produced by HIGT benefit vascular function remains unclear. The impact of HIGT on endothelium-dependent vasodilation, nitrosyl-hemoglobin content (NO-Hb), and insulin sensitivity were studied using aortic ring preparations, electron spin resonance spectroscopy (ESR), homeostasis assessment of insulin resistance (HOMA-IR) calculations, and insulin tolerance testing (ITT). Data were correlated with selected hormone and adipocytokine concentrations. Rats made diabetic with streptozotocin were treated with subcutaneous insulin pellets dosed to sustain body weights and hyperglycemia or with HIGT; nondiabetic rats served as controls. Hyperglycemic rats demonstrated impaired endothelium-dependent vasodilation, reduced levels of NO-Hb, and diminished insulin, leptin, and adiponectin concentrations compared with controls. In contrast, HIGT treatment significantly reduced blood sugars and sustained both endothelium-mediated vasodilation and NO-Hb at control levels. HOMA-IR calculations and ITT indicated enhanced insulin sensitivity among HIGT-treated rats. HIGT partially restored suppressed leptin levels in hyperglycemic rats and increased adiponectin concentrations to supranormal levels, consistent with indicators of insulin sensitivity. Our findings indicate that the metabolic milieu produced by HIGT is sufficient to preserve vascular function in diabetic rodents. These data suggest that improved glycemia, induction of a beneficial adipocytokine profile, and enhanced insulin sensitivity combine to preserve endothelium-dependent vascular function in HIGT-treated diabetic rats. Consequently, HIGT may represent a novel and efficacious approach to reduce diabetes-associated vascular dysfunction.

Acetylcholine↗

PubMed2005

Host cells reduce glucose uptake and glycogen deposition in response to hepatic insulin gene therapy.

BACKGROUND: Hepatic insulin gene therapy (HIGT) restores weight gain and near-normal glycemia in rodent models of insulin-deficient diabetes mellitus. However, the effect of transgenic insulin on endogenous genes and recipient cell function is relatively unexplored. To investigate hepatocellular effects of transgenic insulin expression, we evaluated intermediary glucose metabolism in primary cultured hepatocytes treated with HIGT. METHODS: Rat hepatocytes were transduced with adenovirus expressing a glucose-responsive human insulin transgene and cultured in high-glucose and high-insulin conditions. We determined glycogen content in cell cultures and intact liver directly. Glycogenolysis was compared using glucose production of cultured cells. Glucose uptake, oxidative, and glycolytic processing were determined by radiotracer analysis or direct end-product assessment. Quantitative real-time reverse transcriptase polymerase chain reaction was used to determine expression of glucose transporter 2 (GLUT2) and glucokinase genes. GLUT2 protein abundance was determined by Western blot analysis. RESULTS: HIGT-treated hepatocytes contained significantly less glycogen than either untreated hepatocytes or those treated with an empty virus. Glucose release owing to glycogenolysis remained normal. However, HIGT treatment significantly impaired glucose uptake and processing. Metabolic synthetic processes were not generally inhibited, as indicated by enhanced beta-hydroxybutyrate secretion. While preserving cell viability, HIGT treatment diminished expression of both glucokinase and GLUT2. In HIGT-treated streptozocin-treated diabetic rats, total liver glycogen was intermediate between diabetic animals and normal controls. CONCLUSIONS: These results suggest gene-specific effects in recipient hepatocytes following HIGT treatment and underscore the need for expanded studies examining host cell responses to the transfer of metabolically active transgenes.

Animals↗

PubMed2004

Diabetes in older adults. Overview of AGS guidelines for the treatment of diabetes mellitus in geriatric populations.

The recently published guidelines from the California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes provide recommendations that should help improve care in that population. This paper will summarize the guidelines and indicate which recommendations are evidence-based and which are based on expert opinion, as some aspects of the guidelines have not been examined in controlled clinical trials. Practitioners need to apply approaches to care that consider level of function and the patient's and family's wishes and values.

Aged↗

PubMed2004

Implementing evidence-based diabetes care in geriatric populations. The chronic care model.

The prevalence of diabetes mellitus in older adults continues to increase and their health care is often suboptimal. The chronic care model discussed in this article provides a framework for change in the practice and organization of care for chronic illnesses, including diabetes. This model facilitates optimal care of both individuals and populations, including older adults with diabetes. Evidence-based, clinical interventions that can be implemented in the physician's practice are discussed.

Aged↗

PubMed2003

Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor rats.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in multiple rodent models of diabetes mellitus, with variable degrees of glucose control. We demonstrate here that adenoviral delivery of a glucose-regulated transgene into rat hepatocytes produces near-normal glycemia in spontaneously diabetic BB/Wor rats without administration of exogenous insulin. We compared growth, glycemia, counterregulatory hormones, and lipids in HIGT-treated diabetic rats to nondiabetic rats and diabetic rats treated with either insulin injections or sustained-release insulin pellets. HIGT-treated rats achieved near-normal blood glucose levels within 1 week and maintained glycemic control for up to 3 months. Rats treated with sustained release insulin implants had similar blood sugars, but more hypoglycemia and gained more weight than HIGT-treated rats. HIGT-treated rats normalized blood glucose within 2 hr after a glucose load, and tolerated a 24-hr fast without hypoglycemia. HIGT treatment suppressed ketogenesis similarly to peripheral insulin. However, glucagon levels and free fatty acids were increased in HIGT-treated rats compared to either nondiabetic controls or rats treated with exogenous insulin. In addition to extending successful application of HIGT to a rat model of autoimmune diabetes, these findings emphasize the relative contribution of hepatic insulin effect in the metabolic stabilization of diabetes mellitus.

3-Hydroxybutyric Acid↗