Increase In Islet Blood Flow Research Articles

Stimulation of intestinal glucoreceptors in rats increases pancreatic islet blood flow through vagal mechanisms.

The aim of the study was to evaluate whether intestinal glucoreceptors participate in the regulation of pancreatic islet blood flow. For this purpose, anesthetized rats were infused (0.1 ml/min for 3 min) with saline, glucose, or 3-O-methylglucose directly into the duodenum. The glucose (1 mg/kg body wt) infusion rate was chosen to prevent any effects on systemic or intraportal blood glucose concentrations. Intraduodenal infusion of D-glucose increased both serum insulin concentration and islet blood flow, whereas the osmotic control substance 3-O-methylglucose had no such effects. A bilateral abdominal vagotomy performed before the infusions totally abolished both the insulin and blood flow response to glucose infusion. The absence of an increased islet blood flow in response to glucose infusion in the denervated, transplanted pancreas was a further indication of the crucial importance of the regulation of islet blood flow by the vagus nerves. It is concluded that intestinal glucoreceptors participate in the mediation of glucose-induced islet blood flow increase.

Influence of age, hyperglycemia, leptin, and NPY on islet blood flow in obese-hyperglycemic mice.

This study aimed to elucidate possible age-related changes in islet blood perfusion in lean and obese C57BL/6 mice. Obese mice aged 1 mo were hyperglycemic and hyperinsulinemic and had an increased islet blood flow compared with age-matched lean mice. This augmented blood flow could be abolished by pretreatment with leptin. The islet blood perfusion was, in contrast to this, markedly decreased in obese 6- to 7-mo-old animals compared with age-matched lean mice. Reversal of hyperglycemia, but not hyperinsulinemia, in these obese mice with phlorizin normalized the islet blood flow. Spontaneous reversal of hyperglycemia, but not hyperinsulinemia, was seen in the 12-mo-old obese mice. Islet blood perfusion in obese mice at this age did not differ compared with lean mice. It is suggested that the initial increase in islet blood flow in obese mice is due to the leptin deficiency. The subsequent decrease in islet blood perfusion is probably caused by the chronic hyperglycemia. The described islet blood flow changes may be of importance for impairment of islet function in obese-hyperglycemic mice.

Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats.

An intrinsic angiotensin system has been described in the pancreas, with angiotensin II specific receptors being present on both exocrine, endocrine and vascular cells. The aim of the present study was to evaluate the effects of angiotensin II on insulin secretion and blood flow regulation in the pancreas. Blood flows were determined with a microsphere technique. Infusion of angiotensin II induced a dose-dependent reduction in both whole pancreatic and islet blood flow, which was most pronounced in the former. Administration of enalaprilate, an inhibitor of angiotensin-converting enzyme, and saralasin, a nonselective angiotensin II receptor antagonist, preferentially increased islet blood flow. The effects of angiotensin II on insulin release were examined by measuring insulin concentrations in the effluents from isolated perfused pancreata. In these preparations, enalaprilate affected neither basal nor glucose-stimulated insulin release, whereas angiotensin II delayed the first phase of insulin release in response to glucose. The effect of angiotensin II was probably due to initial marked vasoconstriction. The retardation of insulin release could be avoided by adding angiotensin II to the perfusion medium 20 min before glucose administration, i. e. so that the vasoconstriction had disappeared when glucose-stimulation began. The present study suggests that the angiotensin-system is important in regulation of islet blood flow and points to a pivotal role of islet blood perfusion for an adequate insulin release.

Increased pancreatic islet blood flow in 48-hour glucose-infused rats: involvement of central and autonomic nervous systems.

The pancreatic islet blood flow of rats 24 h after a prolonged (48-h) glucose infusion was investigated using a nonradioactive microsphere technique. In the basal state, islet blood flow was significantly increased in previously hyperglycemic rats (HG) compared to that in controls (C). During an i.v. glucose challenge, both plasma insulin and islet blood flow were increased in the two groups, but these increases were significantly higher in HG than in C rats. Although less pronounced, the results were similar when glucose was injected into the carotid artery toward the brain at a dose that did not modify the peripheral glucose level. The effect of this intracarotid injection was abolished after bilateral subdiaphragmatic vagotomy in both C and HG rats. Furthermore, in the latter group, both plasma insulin concentration and islet blood flow returned to values similar to those observed in the basal state in C rats. After pretreatment with the alpha2-adrenoceptor agonist clonidine, the insulin response to the intracarotid glucose load was totally blunted in the two groups of rats. By contrast, whereas such a pretreatment lowered the glucose-induced increase in islet blood flow in C rats, it was without effect in HG rats. These data suggest that a period of hyperglycemia and/or hyperinsulinemia is sufficient to induce a perturbation of pancreatic islet blood flow, which appears to be mainly due to an increased parasympathetic activity, whereas the decrease in sympathetic tone does not play a role. These modifications in autonomic nervous system activity could be due to alterations in some brain areas involved in "glucose sensing."

Gastric Inhibitory Polypeptide and Splanchnic Blood Perfusion: Augmentation of the Islet Blood Flow Increase in Hyperglycemic Rats

Svensson, A. M., S. Efendic, C.-G. ÖStenson and L. Jansson. Gastric inhibitory polypeptide and splanchnic blood perfusion: Augmentation of the islet blood flow increase in hyperglycemic rats. Peptides 18(7) 1055–1059, 1997.—The aim of the study was to investigate how the incretin candidate hormone gastric inhibitory polypeptide (GIP) affects splanchnic blood flow, especially pancreatic islet blood flow. For this purpose, male Sprague–Dawley rats were injected intravenously with either saline or GIP (5 or 15 μg/kg body weight) 10 min before blood flow measurements by a microsphere technique. Furthermore, 3 min before the blood flow measurements, 1 ml of either saline or 30% d-glucose was given intravenously. All glucose-injected animals were markedly hyperglycemic (>20 mmol/liter) at the time of the blood flow measurements. Both doses of GIP potentiated basal and glucose-stimulated insulin release. In the normoglycemic rats, the lowest dose of GIP did not affect the blood perfusion to any of the investigated organs. The highest dose of GIP decreased whole pancreatic and duodenal blood flow, whereas islet blood flow was unaffected. As a result, fractional islet blood flow was increased. In the hyperglycemic rats, where the islet blood flow was increased compared with control animals, both doses of GIP further enhanced islet blood flow. No effect on pancreatic, fractional islet, or duodenal blood flow was seen after GIP administration to hyperglycemic animals. It is concluded that administration of GIP can further augment the glucose-induced stimulation of islet blood flow. This may contribute to facilitating release of insulin from the islets.

Microsphere distribution in the pancreas of anesthetized rats. Alloxan stimulates the blood flow to all islets whereas glucose only affects the blood perfusion of a subgroup of islets.

Islet blood flow stimulation induced by alloxan leads to an increased blood perfusion in all islets, whereas glucose induces a flow increase only in a subgroup of islets. The aim of the present study was to investigate if an increased islet blood flow was associated with an enhanced total number of perfused islets, or whether only a subgroup of the islets increased their blood flow. For this purpose, the whole pancreatic and islet blood flow was measured with a microsphere technique (4.5 x 10(5) microspheres/kg body wt) in anesthetized Sprague-Dawley rats. Blood flow measurements were made 3 min after an i.v. injection of 1 mL of saline, alloxan (75 mg/kg body wt), or D-glucose (300 mg/mL). Alloxan reduced whole pancreatic blood flow by 50%, but almost doubled islet blood flow. Glucose did not affect whole pancreatic blood flow, but increased islet blood flow 100%. Approximately 10% of the islets in control and glucose-injected rats contained microspheres, compared with about 25% in alloxan-injected rats (P < 0.001). When the islets containing a certain number of microspheres were compared, alloxan induced a homogeneous shift of the curve to the right, i.e., increased the number of islets that contained all amounts of microspheres. Glucose preferentially increased only the fraction of islets containing > or = 3 microspheres.

Glucose-induced islet hyperemia is mediated by nitric oxide

To determine whether hyperglycemia affects pancreatic islet microcirculation in vivo and whether nitric oxide is a mediator. Islet blood flow was measured before and after infusion of glucose during in vivo microscopy of mouse pancreatic islet. The pancreas of male BALB/c mice was exteriorized and viewed under the microscope utilizing monochromatic transmitted light. The carotid artery and tail vein were cannulated and systemic blood pressure was monitored continuously. Under fluorescent light, a 0.02 mL bolus of 2% fluorescein isothyocyanate (FITC-albumin) was injected intra-arterially and the first pulse of FITC-albumin through an islet capillary was videorecorded. Following equilibration, either glucose or normal saline 300 mg/g of body weight was given intravenously. Five minutes later, a second bolus was given and the second pulse was videorecorded. The study was repeated in the presence of N omega-nitro-L-arginine methyl ester (L-NAME). The FITC-albumin bolus mean transit time (TT) and observed cross time (OCT) through the islet were calculated using slow-motion video analysis of the recorded images. Infusion of glucose resulted in a significant increase in islet blood flow with no change in systemic blood pressure: baseline TT was 20 +/- 1.3 pixel/0.03 sec and baseline OCT was 0.6 +/- 0.04 seconds; during hyperglycemia, TT was 16.1 +/- 1 pixel/0.03 sec, and OCT was 0.48 +/- 0.03 seconds (n = 11, P < 0.05 versus basal via paired t-test). Continuous infusion of L-NAME negated the effect of hyperglycemia on islet blood flow: baseline TT was 20 +/- 1.8 pixel/0.03 sec and OCT was and 0.6 +/- 0.05 seconds; during hyperglycemia, TT was 20 +/- 1.1 pixel/0.03 sec and OCT was 0.6 +/- 0.33 seconds (n = 10; P < 0.05 versus glucose via unpaired t-test).

Effects of the biguanide metformin on splanchnic blood flow in rats: preferential and dose-dependent increase in islet blood flow.

The aim of the present study was to evaluate if metformin, a biguanide used in the treatment of noninsulin-dependent diabetes, induced any changes in splanchnic circulation. For this purpose, anesthetized rats were injected intraperitoneally with saline alone (1 ml/kg BW) or metformin (15 or 30 mg/kg BW) 30 min before blood flow measurements. No effects on blood glucose or serum insulin concentrations could be discerned after administration of metformin. Both duodenal, whole pancreatic and islet blood flow were approximately doubled by the lowest dose (15 mg/kg BW) metformin. However, the higher dose (30 mg/kg BW) did not affect duodenal or pancreatic blood flow, whereas islet blood flow was markedly increased also in this group of animals. It is concluded that the blood flow to the pancreatic islets can be specifically enhanced by metformin. To what extent this contributes to the antihyperglycemic action of the drug is presently unknown.

Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic GK rats.

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.

Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic GK rats

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.

Changes in islet blood flow in rats with NIDDM.

Islet blood flow was quantified in NIDDM rats either of the GK strain on after neonatal injection of STZ (n0-STZ), using the non-radioactive microsphere technique. In the basal state, there was a good correlation between plasma insulin level and islet blood flow, i.e. both were increased or decreased in comparison to those of control rats in GK and n0-STZ rats, respectively. The increased islet blood flow and plasma insulin levels observed in the GK rats were abolished by bilateral subdiaphragmatic vagotomy. During a glucose challenge, whereas plasma insulin and islet blood flow were doubled in control rats, these parameters were not modified in the diabetic rats. These data demonstrate an alteration in the islet blood flow of diabetic rats during a glucose challenge which could participate in the abnormal glucose-induced insulin secretion previously described in these two models.

Alloxan, but not streptozotocin, increases blood perfusion of pancreatic islets in rats.

It has recently been shown that selective B-cell toxins alloxan and streptozotocin (STZ) possess marked effects also on the vascular system. To evaluate to what extent changes in blood perfusion of islets induced by alloxan or STZ could be of importance for diabetogenic action of these compounds, we first investigated acute effects of alloxan (75 mg/kg body wt iv) and STZ (40 mg/kg body wt iv) on both whole pancreatic blood flow (PBF) and islet blood flow (IBF) in adult rats. Alloxan caused a marked increase in IBF, which was most pronounced 3 min after administration and remained for 30 min. PBF, however, was decreased 3 min after alloxan administration but was similar to that of control animals from 10 min and onward. These two opposite effects on IBF and PBF caused the fraction of whole PBF diverted through islets to increase from approximately 10 to 50%. Pretreatment with glucose (2 g/kg body wt iv), indomethacin (3.5 mg/kg body wt iv), dimethyl sulfoxide (10 ml/kg body wt ip of a 33% solution), superoxide dismutase (SOD, 1,000 kU/kg body wt iv), NG-methyl-L-arginine (30 mg/kg body wt iv), theophylline (7 mg/kg body wt iv), or terbutaline (1 mg/kg body wt iv) failed to affect stimulation of IBF by alloxan observed at 3 min. SOD was found to exert a marked stimulation of IBF both when given alone and together with alloxan. Alloxan increased IBF and decreased PBF also in a syngeneic pancreaticoduodenal graft in rats but did not affect flow distribution in a perfused pancreas-duodenum preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased islet blood flow in obese rats: role of the autonomic nervous system.

Hyperinsulinemia, a main feature of both human and animal obesity, has been demonstrated to be due to both an increased sensitivity to nutrient secretagogues and an impairment of the nervous regulation of insulin secretion. Recent studies have shown that pancreatic islet blood flow increases under conditions associated with an enhanced insulin secretion. The aim of this study was to determine whether or not changes in islet blood flow are present in hyperinsulinemic obese rats. Using the nonradioactive microsphere technique, we were able to show a significantly higher islet blood flow in obese rats either of the Zucker strain or Wistar rats after lesion of the ventromedial hypothalamus than in their respective lean controls. Subdiaphragmatic vagotomy had no significant effect on basal islet blood flow of lean rats, whereas it decreased significantly that of obese Zucker rats. Conversely, clonidine, an alpha 2-adrenergic agonist, induced a higher decrease of islet blood flow in obese than in lean Zucker rats. The injection of an intravenous bolus of glucose (375 mg/kg iv) increased significantly more islet blood flow in obese than in lean Zucker rats. It is concluded that obese rats present an increased pancreatic islet blood flow, which may result, at least in part, from exaggerated parasympathetic activity and lower than normal sympathetic activity. This could participate in the hyperinsulinemia observed in these rats.

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were higher than in S-rats (p less than 0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p less than 0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.

Altered blood flow regulation in autotransplanted pancreatic islets of rats

Adult rats were partially depancreatized, and approximately 500 islets were isolated from each excised pancreas, maintained in tissue culture for 7 days, and subsequently transplanted back to the same animals beneath the renal capsule. Four weeks after transplantation the animals were anesthetized and given an intravenous injection of 1 ml of either saline, 30% (wt/vol) D-glucose, 30% (wt/vol) D-galactose, DL-propranolol (15 mg/kg body wt) dissolved in saline, or terbutaline (1 mg/kg body wt) dissolved in saline. Five minutes later blood perfusion of the islet grafts and the pancreatic remnant were measured with a microsphere technique. Islet blood flow was also measured in animals with pancreas intact and no islet grafts after administration of saline, glucose, or galactose. These animals demonstrated a significant and preferential increase in islet blood flow after glucose administration, whereas galactose caused a selective decrease in islet blood perfusion. Both whole pancreatic blood flow and islet blood flow in the pancreatic remnant were decreased by terbutaline administration, whereas the other substances had no effect. Blood flow to the transplanted islets was decreased by glucose and galactose, whereas propranolol and terbutaline had no effect compared with the saline-injected animals. These results suggest that blood flow regulation differs between transplanted pancreatic islets, islets in the normal pancreas, and islets in the pancreatic remnant after partial pancreatectomy. Whether this reflects lack of innervation or an altered reactivity of the newly formed blood vessels in islet grafts is presently unknown.

Age-dependent changes of pancreatic islet blood flow in the rat.

Whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured in anesthetized Sprague-Dawley rats aged 5, 20, 52, or 104 wk. PBF decreased progressively with age, from approximately 0.55 mL x min-1 x g pancreas-1 in 5- and 20-wk-old rats to 0.30 mL x min-x g pancreas-1 in 52- and 104-wk-old rats. In animals aged 5 wk, the IBF was approximately 25 microL x min-1 x g pancreas-1 but increased to about 60 microL x min-1 x g pancreas-1 (p less than 0.001) in animals aged 20-104 wks. When IBF was expressed as a fraction of PBF, a different pattern was observed. In the 5-wk-old animals only 5% (p less than 0.001) of the PBF flowed through the islets, whereas the rats aged 20 wk had a fractional IBF of about 10%. A significantly larger fraction, of approximately 20%, was diverted through the islets in the 52- and 104-wk-old rats. Glucose administration to animals aged 5, 20, and 52 wk significantly increased both PBF and IBF, but had a more marked effect in the older animals. The fractional IBF was also increased by glucose in the two latter groups, indicating a preferential increase in IBF. In the animals aged 5 wk, however, PBF and IBF increased in concert. We conclude that the previously described age-dependent changes in islet volume and functional capacity of the islet organ is also accompanied by changes in the IBF.

Intrinsic regulation of the blood flow to the endocrine and exocrine parts of the rat pancreas.

To evaluate possible differences in the local regulation of blood flow between the endocrine and exocrine pancreatic parenchyma, the blood perfusion of the pancreas and the pancreatic islets has been measured after a 90-second period of anoxia or a 5-min period of increased venous pressure. After anoxia, caused by interruption of arterial blood flow, there was a significant increase (P less than 0.01) in islet blood flow (IBF) while whole pancreatic blood flow (PBF) remained unchanged. Arterial occlusion also increased the serum glucose (P less than 0.01) and serum insulin concentrations (P less than 0.001). Vagotomy prevented the increase in IBF but did not affect the increase in serum glucose or serum insulin concentration, which suggests that the increase in IBF was due to the increased serum glucose concentration. An increased venous pressure in the portal vein did not affect IBF, PBF, serum glucose or serum insulin concentrations. It is concluded that, in the rat pancreas, the local control of PBF and IBF is of minor importance in the regulation of blood flow.

Glucose-induced changes in pancreatic islet blood flow mediated by central nervous system.

Earlier experiments with the microsphere technique suggested that a heightened serum glucose concentration consistently leads to an increase in islet blood flow (IBF). Several lines of evidence suggest that this glucose-sensitive control mechanism is located at an extrapancreatic site. The purpose of this study was to define the possible role of the central nervous system in such a mechanism. D-glucose, L-glucose, 3-O-methylglucose, or saline were therefore infused into the carotid artery, each at a dose of 1 mg X kg body wt-1 X min-1 for 3 min, and the pancreatic and islet blood flows were measured. None of these substances affected the systemic serum glucose level. The intracarotid infusion of D-glucose, however, caused a rapid increase in both the serum insulin concentration and IBF. The blood flow to the whole pancreas nevertheless remained unchanged, indicating a redistribution of flow within the gland. Carotid infusion of the other test substances or a similar amount of D-glucose given in a femoral vein did not affect these parameters. Both the increase in serum insulin concentration and the increase in IBF caused by D-glucose could be abolished by vagotomy or administration of atropine. When the systemic blood glucose concentration was increased by intraperitoneal glucose administration (2 g/kg body wt), vagotomy blocked the increase in islet blood flow but not the concomitant insulin release. These observations suggest that the glucose-induced increase in IBF is mediated by vagal cholinergic influences.

Dissociation between pancreatic islet blood flow and insulin release in the rat.

The blood flow to the pancreatic islets was estimated with the aid of microspheres in fed or starved (72 h) rats. The total pancreatic blood flow (PBF) in fed animals was 0.55 +/- 0.04 ml X min-1 X g pancreas and in the starved animals 0.30 +/- 0.04 ml X min-1 X g pancreas (P less than 0.001), and the corresponding islet blood flow (IBF) 82.0 +/- 12.4 and 50.5 +/- 9.7 microliter min-1 X g pancreas respectively (P greater than 0.05). Intraperitoneal injection of 2 ml of a 30% glucose solution caused a marked increase in IBF in both fed (P less than 0.05) and starved (P less than 0.01) animals to approximately the same level. The circulating insulin concentration remained unaffected by glucose in the starved rats but increased (P less than 0.001) in the fed rats, indicating that insulin release does not necessarily rise in parallel with an elevated IBF. Intraperitoneal injection of 2 ml of a 30% solution of mannoheptulose, an inhibitor of islet glucose metabolism, decreased the serum insulin concentrations although the serum glucose concentrations rose significantly in both fed (P less than 0.001) and starved (P less than 0.001) animals. This treatment, however, caused both IBF and PBF to increase significantly in both groups. The data support the view that islet blood flow is not necessarily related to the metabolic status of the islet cells or to the insulin release.

Stimulation by glucose of the blood flow to the pancreatic islets of the rat.

Blood flow to the pancreatic islets of the rat was estimated with the microsphere technique. Experiments with microspheres of different sizes (diameter 10, 15 or 50 micron) showed that optimal results were obtained with 10-micron spheres. Localization of microspheres either within or outside the islets was accomplished by freeze-thawing of the pancreas, making it transparent, so that both islets and microspheres could be distinguished in dark field illumination. Thus, microscopic examination of the freeze-thawed pancreas allowed the microspheres to be counted separately in both the endocrine and exocrine parenchyma. Under basal conditions, pancreatic blood flow was calculated as 0.60 ml X min-1 X g-1 (w/w). The islets accounted for about 10% of the total pancreatic blood flow, corresponding to 0.069 ml/min per whole pancreas. A bolus dose of glucose increased pancreatic blood flow to 0.75 ml X min-1 X g-1 (p less than 0.05), while the fractional islet blood flow rose to 15.1% (p less than 0.001) corresponding to 0.125 ml X min-1 X pancreas-1 (p less than 0.001). The glucose-induced increase in pancreatic blood flow mainly resulted from increased flow to the pancreatic tail, while the corresponding increase in islet blood flow was uniformly distributed throughout the pancreas. Injection of the non-metabolizable glucose-derivate. 3-0-methyl-D-glucose, affected neither the pancreatic nor the islet blood flow. The data indicate that the islets receive more of the pancreatic blood flow than would be accounted for by their relative volume and that glucose preferentially stimulates blood flow to the islets.