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Biomedical subjects

A E Freedlender

Publications and source records attributed to A E Freedlender.

9 recordsLinked to original sources
PubMed1992

The effect of pancreatic polypeptide on glucose disposal after surgical alterations of the pancreas.

Surgical alterations of the pancreas result in anatomic changes that can affect postoperative glucose metabolism. Pancreas transplantation results in reduction of beta-cell mass, systemic release of insulin, and denervation. The authors hypothesized that such alterations affect peripheral glucose disposal to induce an "insensitivity" to endogenously (systemically) released insulin. Additionally, they hypothesized that surgically induced deficiency of the postprandial hormone, pancreatic polypeptide, might contribute to altered glucose disposal. The authors studied two surgical models in dogs known to be devoid of pancreatic polypeptide--70% proximal pancreatectomy (PPx) and PPx plus distal pancreas autotransplantation (PAT/B). Oral glucose challenge and euglycemic hyperinsulinemic clamp studies were performed before and after a 16-day "pulsed" infusion of pancreatic polypeptide. Both surgical procedures resulted in elevations in the integrated glucose response after oral glucose, which was not affected by pancreatic polypeptide infusion. Euglycemic clamp studies showed decreased hepatic glucose output (Ra) and overall glucose disposal (Rd) in the fasted state for both surgical groups. The transplant animals demonstrated significant decreases in Rd during the hyperinsulinemic challenge (3.2 +/- 0.01 versus 5.7 +/- 0.01 mg/kg/minute at 60 to 120 minutes for PAT/B versus control). After 16 days of pancreatic polypeptide infusion, however, basal Ra, as well as basal and 60- to 120-minute Rd values, were returned to control values in the transplant group. The authors conclude that pancreas transplantation results in altered glucose disposal, possibly due to an altered effectiveness of systemically released insulin. They conclude that pancreatic polypeptide is an important modulator of peripheral insulin action. Therefore, the role of pancreatic polypeptide must be taken into account when evaluating postoperative glucose metabolism in canine models of pancreas transplantation.

Animals↗
PubMed1991

Glipizide treatment of pancreas autotransplantation: effects on alterations in glucose-insulin relationships.

Pancreas transplantation has been proven effective in supplying an endogenous insulin supply in diabetics. However, alterations in glucose metabolism after transplantation suggest a possible "insensitivity" to its action in the periphery. We hypothesized that sulfonylurea treatment of canines who had received segmental pancreas autotransplants would correct these alterations by altering peripheral insulin sensitivity. Glipizide therapy (5 mg p.o. b.i.d.) did appear, in fact, to enhance basal insulin sensitivity by lowering fasting glucose (100 +/- 3 to 81 +/- 11 mg/dl pre-treatment to post-treatment) while not affecting basal insulin levels. However, glipizide therapy was associated with decreased insulin response to challenge by either oral glucose (2 gm/kg) or sustained intravenous hyperglycemia (150 mg/dl above basal). We conclude that our model of pancreas autotransplantation documents alterations in glucose metabolism which are devoid of the effect of immunosuppression. Glipizide treatment appears to affect fasting sensitivity to insulin, but results in a decrement of insulin response to oral or intravenous glucose challenge.

Animals↗
PubMed1989

Insulin-dependent and insulin-independent effects after surgical alterations of the pancreas.

Anatomic alterations of the pancreas result in physiologic alterations that have not been completely analyzed. Insulin plays a major role in carbohydrate metabolism; nevertheless, as much as 50% of a hyperglycemic load may be metabolized independent of insulin. We analyzed the effects of surgical alterations of the pancreas on postoperative glucose metabolism, including insulin-independent effects. Mongrel female dogs underwent one of three procedures: proximal partial pancreatectomy (PPx), PPx plus diversion of pancreatic venous effluent to the systemic circulation (SC), or PPx plus segmental pancreatic autotransplantation (PAT). Intravenous glucose tolerance tests, with or without a background infusion of somatostatin (SST; 400 ng/kg/min) were performed on all animals preoperatively and postoperatively. SST completely suppressed secretion of assayable peripheral insulin. The rate of glucose disposal during SST suppression approximates the rate of insulin-independent glucose disposal (IIGD). Although there was a significant decrease in the rate of glucose disposal during SST infusion when compared with the rate without SST, no differences in IIGD were found between postoperative groups. IIGD was calculated at 50% to 55% for control, PPx, and SC groups and at 67% for PAT. Peripheral sensitivity to an exogenous insulin infusion (euglycemic clamp) was unchanged by any of the procedures. We conclude that surgical alteration of the pancreas, including pancreas transplantation, results in altered glucose handling in the face of "normal" peripheral levels of insulin. Changes in IIGD and analysis of peripheral sensitivity to insulin do not explain these alterations completely.

Animals↗
PubMed1988

Peripheral insulin release after pancreatic resection: the effect of decreased beta-cell mass with systemic or portal drainage.

Surgical alteration of the pancreas can result in several anatomic alterations which may affect insulin release. We evaluated the effects of resection, systemic drainage, and autotransplantation of the canine pancreas on peripheral insulin levels and glucose disposal as measured by iv glucose tolerance tests (IVGTT) and a steady state hyperglycemic challenge (clamp). Proximal pancreatectomy (PPx) with reduced beta-cell mass and intact portal drainage resulted in a modestly elevated fasting glucose level and increased integrated glucose response to IVGTT. Compared to preoperative normals, basal insulin was unchanged from preoperative controls; however, peak insulin and integrated insulin response to IVGTT were decreased in PPx animals. Splenocaval drainage or autotransplantation of the distal pancreas resulted in normalization of the severely altered insulin response and fasting glucose levels. K values were significantly reduced after all three procedures. Clamp studies confirmed the basal glucose and insulin findings of the IVGTT. During the clamp, PPx animals had peripheral insulin values approximately 50% of normal controls, while autotransplantation and splenocaval drainage animals had insulin values that approximate normal controls. All three postsurgical groups had blunted insulin levels during stable hyperglycemia. Glucose utilization rates were severely decreased in all three groups. Reduction of beta-cell mass with intact portal drainage resulted in reduced insulin response to glucose challenge by either IVGTT or clamp. Systemic drainage of this same reduced beta-cell mass resulted in peripheral insulin levels comparable to normal controls. Denervation (autotransplantation) had little additive effect. All three groups demonstrated severely decreased rates of glucose disappearance as measured by both IVGTT and clamp studies. Therefore, reduction in beta-cell mass, drained systemically or portally, results in altered glucose disposal regardless of the peripheral insulin levels.

Animals↗
PubMed1983

Control of renal function by intrarenal angiotensin II.

The purpose of this study was to determine if endogenous angiotensin II affects renal function in conscious dogs after sodium restriction. Intrarenal infusion of the angiotensin receptor antagonist saralasin at doses between 0.13 and 2.5 micrograms/kg X min rapidly attenuated pressor responses produced by systemic injections of angiotensin I over a 90-min period. In contrast, intrarenal infusion of the peptide antagonist at 0.07 microgram/ kg X min did not alter the pressor response to injected angiotensin I. Infusion of angiotensin II into the kidney at 0.1 microgram/min reduced urine output by 50% and was totally inhibited by simultaneous infusion of 0.07 micrograms/kg X min saralasin. Intrarenal infusion of saralasin at 0.07 micrograms/kg X min into sodium-restricted conscious dogs increased effective renal plasma flow, glomerular filtration rate, and sodium, potassium and water excretion, whereas urine osmolarity and free water formation were unchanged. These data demonstrate that saralasin can be effectively confined to the renal mass after intrarenal infusion at a dose capable of inhibiting angiotensin action and that endogenous angiotensin plays an important role in maintaining renal function after sodium restriction.

Angiotensin I↗
PubMed1982

Elevated intra-abdominal pressure and renal function.

The effect of increased intra-abdominal pressure on cardiac output and renal function was investigated using anesthetized dogs into whom inflatable intraperitoneal bags were placed. Hemodynamic and renal function measurements were made at intra-abdominal pressures of 0, 20, and 40 mmHg. Renal blood flo and glomerular filtration rate decreased to les than 25% of normal when the intra-abdominal pressure was elevated to 20 mmHg. At 40 mmHg intra-abdominal pressure, three dogs became anuric, and the renal blood flow and glomerular filtration rate of the remaining dogs was 7% of normal, while cardiac output was reduced to 37% of normal. Expansion of the blood volume using Dextran-40 easily corrected the deficit in cardiac output, but renal blood flow and glomerular filtration rate remained less than 25% of normal. Renal vascular resistance increased 555% when the intra-abdominal pressure was elevated from 0 to 20 mmHg, an increase fifteen-fold that of systemic vascular resistance. This suggests that the impairment in renal function produced by increased intra-abdominal pressure is a local phenomenon caused by direct renal compression and is not related to cardiac output.

Abdomen↗
PubMedDate not supplied

Importance of plasma angiotensin concentrations in a comparative study of responses to angiotensin in the maturing newborn lamb.

Plasma angiotensin concentrations were measured in a longitudinal study of the vascular, renal, and adrenal responses to infusions of angiotensin II (AII) in the maturing newborn lamb. Basal plasma concentrations of angiotensin increased with age and correlated with the rising arterial pressure that occurred with maturation. However, age was a stronger determinant of arterial pressure than was plasma angiotensin concentration. For any given dose of AII per kilogram of body weight, the actual plasma angiotensin concentration achieved increased as the lambs matured and gained weight. Therefore, a comparative study of biologic responses to AII in maturing animals must be based on actual plasma angiotensin concentrations achieved rather than on dose of AII infused per kilogram of body weight. When analyzed on the basis of actual plasma angiotensin concentration, the increase in arterial pressure and the suppression of plasma renin activity in response to increasing plasma angiotensin concentrations did not differ significantly as the lambs matured. However, the increment in plasma aldosterone concentrations in response to increasing plasma angiotensin concentrations was diminished in immature lambs (less than 18 days) when compared to the aldosterone responses in the same lambs at older ages.

Aging↗
PubMedDate not supplied

Measurement of glycosylated hemoglobins using boronate affinity chromatography.

A boronate affinity column method for the measurement of glycosylated hemoglobins was evaluated. In the procedure the glycosylated hemoglobins were bound by immobilized boronic acid to separate them from nonglycosylated hemoglobins. Elution of bound glycosylated hemoglobins was carried out with sorbitol buffer, and the absorbance was read at 414 nm. The method was linear to a glycosylated hemoglobin concentration of at least 20 percent. The precision of the method ranged from 1.2 to 2.8 percent (C.V.) within-run, and 3.4 to 5.3 percent day-to-day. The reference interval was 4.8 to 6.4 percent. The method correlated with a cation exchange resin mini-column method (r = 0.94) and a colorimetric method (r = 0.93) but results from the boronate affinity method were higher in diabetic patients. The measured glycosylated hemoglobin was significantly correlated with estimated one-day-mean plasma glucose in diabetic patients (r = 0.54, n = 52, p less than 0.002). The affinity method provides an attractive alternative to earlier methods for measuring glycosylated hemoglobins.

Adolescent↗