PubMed Health⌕ Search

Biomedical subjects

S Bonner-Weir

Publications and source records attributed to S Bonner-Weir.

At least 127 records · Page 7Linked to original sources
PubMed1985

Pancreatic islets of variable size--insulin secretion and glucose utilization.

Glucose metabolism and insulin secretion were studied in isolated rat pancreatic islets of different sizes and the amount of tissue was quantitated by the measurement of DNA. It was found that larger islets (140-210 ng DNA/islet) utilized more glucose (based on the conversion of 3H-5-glucose to [3H]20) per ng of DNA than islets containing less DNA (60-120 ng/islet). However, the insulin secreted per ng of DNA in response to a given glucose concentration was the same in islets of all sizes. Also, the islet insulin and glucagon content when expressed in terms of DNA did not depend upon islet size. Thus, although glucose utilization rates expressed as a function of islet DNA content were greater in larger islets, no such relationship was found for glucose-induced insulin release or insulin and glucagon content.

Animals↗
PubMed1985

Pancreatic somatostatin.

This is a review of pancreatic somatostatin which is limited in its scope and therefore focuses upon some selected issues. Throughout the entire review the same basic questions recur: Why do islets contain somatostatin? What is the physiological role of somatostatin and what does this peptide have to do with diabetes? Clear answers to these questions do not emerge, but a number of hunches are explored. The review provides a very brief look at somatostatin secretion, a discussion of the potential interactions which islet D cells might have with other islet cell types, consideration of how knowledge of islet anatomy may help us understand the D cell, and finally some comments about what happens to the D cell in diabetes and fasting.

Animals↗
PubMed1985

Impaired insulin biosynthetic capacity in a rat model for non-insulin-dependent diabetes. Studies with dexamethasone.

These studies of a rat model for non-insulin-dependent diabetes mellitus (NIDDM) were performed to determine whether hyperglycemia occurs when capacity to synthesize insulin is exceeded. The neonatal streptozocin (STZ)-treated rat has acute hyperglycemia with marked destruction of pancreatic beta-cells, followed by gradual regeneration to 50-70% normal beta-cell number. At age 4 wk, fed serum glucose concentration is only mildly elevated relative to controls. With age, the rats become progressively hyperglycemic, and by 12 wk they have marked impairment of glucose-stimulated insulin release. In these studies, dexamethasone (0.125 mg/kg/day for 4 days) was administered to control and to STZ-treated animals to produce insulin resistance. The relationship between insulin biosynthesis and serum glucose concentrations was assessed. In control rats, response to dexamethasone was similar at both 4 and 12 wk. Serum glucose levels and pancreatic insulin concentration remained unchanged. Both insulin biosynthetic rates (as measured by 3H-leucine incorporation into proinsulin) and proinsulin mRNA levels increased twofold. STZ-treated rats at age 4 wk demonstrated mild hyperglycemia. Dexamethasone injection resulted in an increase in insulin biosynthesis and proinsulin mRNA in these animals, while serum glucose did not increase. STZ-treated rats at 12 wk showed more profound hyperglycemia (serum glucose 315 +/- 38 mg/dl versus control, 187 +/- 12 mg/dl). A marked rise in serum glucose (to 519 +/- 42 mg/dl) was observed after 4 days of dexamethasone injection. Pancreatic insulin content became severely depleted relative to saline-injected, STZ-treated animals, and there was no response of levels of proinsulin mRNA.

Animals↗
PubMed1985

Abnormal insulin secretion in a streptozocin model of diabetes. Effects of insulin treatment.

We have proposed that chronic hyperglycemia causes the abnormal glucose influence on arginine-stimulated insulin secretion in the neonatal streptozocin (STZ) rat model of NIDDM and therefore studied the effect of 24 h of mild insulin-induced hypoglycemia on this defect. Ultralente insulin, 20 U/kg, was given at 9 a.m. and 10 U/kg at 5 p.m., and insulin and glucagon secretion were then studied the next morning using the in vitro isolated, perfused pancreas. The fed plasma glucose concentrations decreased in the STZ rats from 191 +/- 13 to 101 +/- 9 mg/dl and from 133 +/- 4 to 99 +/- 8 mg/dl in the controls. As expected, 10 mM arginine caused a trivial insulin response at 2.8 mM glucose in the treated and untreated control groups compared with the marked one at 16.7 mM. The response to arginine at 2.8 mM glucose in the untreated STZ rats, however, was strikingly elevated (7.65 +/- 2.29 versus 0.41 +/- 0.16 ng/ml in the untreated controls) and it was not potentiated by the high glucose background, but the result at 2.8 mM glucose in the treated STZ rats was similar to that of the treated controls (0.46 +/- 0.12 versus 0.16 +/- 0.03 ng/ml). A return of glucose influence on IBMX-stimulated insulin secretion was also noted. Glucose-induced insulin release, however, was not restored in the treated STZ rats, but it was markedly suppressed in the controls by the insulin treatment. Glucose influence on the glucagon response to arginine was maintained in the STZ model even though the glucagon release to a lowered glucose concentration was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1984

An in vivo analysis of pancreatic protein and insulin biosynthesis in a rat model for non-insulin-dependent diabetes.

The purpose of these experiments was to estimate insulin biosynthesis in vivo in a rat model for non-insulin-dependent diabetes. Insulin biosynthesis rates were determined in 4-wk-old animals that had been injected with 90 mg/kg of streptozotocin 2 d postpartum. Control and diabetic animals did not differ in body weight or fasting plasma glucose. Fed plasma glucose was significantly elevated (186 +/- 13 micrograms/dl vs. 139 +/- 7 mg/dl, P less than 0.05) and pancreatic insulin content was reduced (41 +/- 2 micrograms/g vs. 63 +/- 8 micrograms/g, P less than 0.05) in the diabetic rats. Insulin biosynthesis was estimated in vivo by measuring and comparing [3H]leucine incorporation into proinsulin with that into total pancreatic protein 45 min after injection. Insulin biosynthesis was 0.391 +/- 0.07% of pancreas protein synthesized in control rats and 0.188 +/- 0.015% (P less than 0.05) in diabetic rats. In animals of the same age, the fractional and absolute rate of pancreatic protein synthesis were determined. Total pancreatic protein synthesis was not reduced in streptozotocin treated animals (185.5 +/- 14.1%/d vs. 158.6 +/- 14.9%/d, NS) but was markedly reduced in control rats after a 48-h fast (to 70.8 +/- 5.5%/d, P less than 0.01). Because total pancreatic protein synthesis was not decreased in the diabetic rats, the decrease in the fraction of radiolabel incorporated into insulin seems to represent an absolute decrease in the rate of insulin biosynthesis in this animal model for diabetes. Through RNA blot hybridization with 32P-labeled cloned rat insulin complementary DNA, proinsulin messenger RNA (mRNA) was estimated as the rate of insulin biosynthesis in control and diabetic animals. There was a 61% reduction in proinsulin mRNA at 4 wk and an 85% reduction at 7 wk (P less than 0.001) in the diabetic animals. After streptozotocin injection in neonatal rats, there is marked beta-cell damage and hyperglycemia. Beta-cell regeneration occurs with return to normoglycemia, but with age hyperglycemia develops. The reduction in insulin synthesis and proinsulin mRNA seemed disproportionate with the more modest reduction in beta-cell number. The importance of these observations is that, in this animal model, diabetes is associated with a limited ability to regenerate beta-cell mass and to synthesize insulin. The relationship between the defect in glucose-stimulated insulin release and impaired insulin biosynthesis has yet to be determined.

Animals↗
PubMed1984

Abnormal islet and adipocyte function in young B-cell-deficient rats with near-normoglycemia.

Sprague-Dawley male rats were injected at 2 days of age with streptozotocin (SZ). At 4 wk of age the fed plasma glucose concentration of the SZ group was 151 +/- 6 mg/dl as compared with 133 +/- 4 for the control group. The fed plasma insulin values were indistinguishable, however. In response to an intraperitoneal glucose challenge the SZ group had marked glucose intolerance and virtually no rise in plasma insulin. After a meal challenge the SZ group also had glucose intolerance, but plasma insulin responses were similar to those of the control. The pancreata of the 4-wk-old rats were perfused in vitro and the SZ group had essentially no response to glucose, but did respond to arginine. Adipocytes of the 4-wk-old SZ rats had impaired glucose conversion to CO2 similar to that seen in the more hyperglycemic 6-wk-old SZ rats. Castration carried out at about 3 wk of age did not influence the hyperglycemia seen at 6 wk of age and later. These data indicate that 4-wk-old SZ rats, while having near-normal plasma glucose levels and normal plasma insulin values, have clearly abnormal B-cell and adipocyte function. With increasing age and weight gain these SZ rats develop frank hyperglycemia.

Adipose Tissue↗
PubMed1984

Abnormal glucose regulation of insulin secretion in models of reduced B-cell mass.

The influence of glucose on nonglucose-stimulated insulin secretion was examined in two animal models with reduced B-cell mass: rats treated with streptozotocin as neonates (SZ) and rats with a partial pancreatectomy (Px). The effects of arginine and IBMX upon insulin secretion were studied at varying glucose concentrations using the in vitro, isolated, perfused pancreas. In normal rats, as expected, 16.7 mM glucose caused a biphasic insulin release and arginine-stimulated insulin secretion was markedly potentiated by an increase in background glucose concentration. In the SZ model, 16.7 mM glucose caused a minimal insulin response. However, arginine stimulated insulin release at 2.8 mM glucose as well as at higher glucose concentrations. A similar alteration in the glucose regulation of insulin secretion was shown with another secretagogue, IBMX, even though responses to this agent in the SZ rats exceeded those of the controls at both high- and low-background glucose concentrations. The less diabetic, Px model showed partial preservation of the glucose regulation of the B-cell response to arginine. Thus, a reduction in B-cell mass leads not only to a loss of glucose-stimulated insulin secretion but also to impaired glucose regulation of nonglucose-stimulated insulin secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release.

To define the consequences of a known reduction of B cell mass in rats, 90% partial pancreatectomies were performed. For the 6 wk following surgery moderate hyperglycemia was maintained in the fed state but there were no differences in body weight nor plasma insulin concentrations compared with sham-pancreatectomized controls. 8-10 wk following surgery regeneration of the remnant was evident with remnant weight being 26%, B cell mass being 42%, and non-B cell mass being 47% of values found for control whole pancreas. There were comparable increases in the remnant content of insulin, glucagon, and somatostatin. Following meal challenges, intraperitoneal and intravenous glucose tolerance tests and intravenous arginine challenge given 6-7 wk after surgery, the insulin responses to glucose were blunted or absent but the responses following the meals or arginine were intact. Similarly, when the pancreatic remnant was perfused in vitro, insulin release after challenge with 300 mg/dl glucose was markedly reduced whereas intact responsiveness to 10 mM arginine was retained. These data suggest that the chronic stimulation of a reduced B cell mass can lead to a selective loss of glucose-induced insulin secretion.

Animals↗
PubMed1983

Elevated proinsulin biosynthesis in vitro from a rat model of non-insulin-dependent diabetes mellitus.

Rats were injected with streptozotocin at 2 days of age. After 10-14 wk, the injected rats showed normal body weight with only modestly elevated fed plasma glucose (controls: 118 mg/dl, diabetic rats: 209 mg/dl). No significant difference between control and diabetic rats was found for overnight fasting plasma insulin levels. The diabetic rats had a retarded rate of disposal of intravenously injected glucose, with only 13% of the incremental increase in plasma insulin seen in control rats 2 min after glucose injection. The immunoreactive insulin content of islets isolated from the diabetic rats was 14% of controls. However, these islets had 74% of the B-cell composition of controls, as estimated by quantitative morphometry. Insulin release (30 min) was lower from islets from diabetic rats than from controls, but was not lowered to the same extent as islet insulin content. Proinsulin biosynthesis was estimated by measuring the incorporation of [3H] leucine or of [3H] phenylalanine into immunoprecipitable material. Proinsulin biosynthesis was strikingly elevated in islets from diabetic rats. Although incorporation of labeled amino acids into total islet protein was also elevated for islets from diabetic rats, the elevation was less pronounced than for incorporation into immunoprecipitable material. The diabetic state of these animals is thus associated with glucose intolerance in vivo, and an increased rate of insulin turnover in isolated islets studied in vitro.

Amino Acids↗
PubMed1982

New perspectives on the microvasculature of the islets of Langerhans in the rat.

The vasculature of the islets of Langerhans was studied in rats using methacrylate corrosion casts and islet reconstructions from stained serial paraffin sections. In corrosion casts, which allowed a three-dimensional view of the pancreatic vasculature, all islets had one or two afferent arterioles, which gave off numerous capillaries to form a glomerular-like network. Islets could be grouped in three classes on the basis of size. Moreover, these classes had preferential locations within the vascular tree: the smaller the islet, the more peripheral. In small islets (those less than 160 micrometers in diameter) efferent capillaries arose from this network and either coalesced at the periphery of the islet or passed through perinsular exocrine tissue before coalescing into venules. However, in intermediate islets (those 160--260 micrometers in diameter) and large islets (those greater than 260 micrometers in diameter) efferent capillaries usually coalesced at the edge of the islet forming an extensive fingerlike network of collecting venules over the islet. This suggested that at least in the rat a large amount of the islet tissue is directly drained by venules. In serial paraffin sections of islets perfused with India ink and stained alternately for B-cells or for non-B-cells, the relation of the blood vessels and the organized array of different cell types making up the islet was discernible. In islets of all sizes, the afferent arterioles entered the islet of all sizes, the afferent arterioles entered the islet at discontinuities of the mantle of non-B-(glucagon, somatostatin, and pancreatic polypeptide) cells. Entering at the B-cell mass, the arterioles broke into capillaries that traversed the B-cell core before passing through the opposite non-B-cell mantle. The afferent capillaries coalesced into collecting venules outside the islet. In intermediate and large islets, the overlying collecting venule network was closely apposed to the mantle. These anatomic findings indicate that in the rat islet only some of the efferent vessels are part of a insuloacinar portal system and that the afferent vessels reach the B-cell core without passing through the non-B-cell islet tissue.

Animals↗
PubMed1981

Responses of neonatal rat islets to streptozotocin: limited B-cell regeneration and hyperglycemia.

Streptozotocin (SZ) was given to 2-day-old neonatal rats, and, during their subsequent development, the interrelationships between plasma glucose, plasma insulin, pancreatic islet morphology, and hormone content were examined. At 4 days of age, a peak of hyperglycemia was observed (SZ, 349 plus or minus 8 mg/dl versus control (C), 127 plus or minus 2) that was associated with a marked reduction of B-cell numbers (SZ, 26.5 plus or minus 2.6% B-cell per islet versus C, 72.8 plus or minus 0.8%). By 10 days of age the SZ animals became normoglycemia with partial recovery of the B-cell number (SZ, 39.6 plus or minus 2.1% versus, C, 64.0 plus or minus 2.6%). By six weeks hyperglycemia returned (SZ, 345 plus or minus 5.2 mg/dl versus C, 171 plus or minus 6.2) with B-cell number of the SZ being 72% of the C (SZ, 48.8 plus or minus 2.4% versus C, 67.5 plus or minus 1.5%). This hyperglycemia and reduced B-cell number persisted to at least 13 wk age. Despite a marked reduction of pancreatic insulin content observed during development, there was little effect upon glucagon or somatostatin content. At 6 wk of age, the plasma insulin concentration was only 30% of C, which suggests as insulin secretory defect beyond that which could be accounted for by the modest B-cell reduction. The present study indicates that even though active regeneration of B-cells occurred after early injury, the capacity for ultimate normalization was limited. The resultant moderate reduction in B-cell number may be associated with a functional defect in glucose-stimulated insulin secretion.

Aging↗
PubMed1981

Islet secretion in a new experimental model for non-insulin-dependent diabetes.

An animal model of diabetes mellitus has been developed in which neonatal rats are injected with streptozotocin at 2 days of age. After transient hyperglycemia followed by near normal glycemia, these animals develop nonketotic diabetes at about 6 wk of age that does not require insulin treatment. Secretion form the endocrine pancreas of 6-15-wk-old rats was evaluated with the isolated, perfused pancreas technique. Insulin secretion responded very poorly to high perfusate glucose concentrations, but in the presence of theophylline this meager response was enhanced. In contrast, arginine elicited an insulin response comparable to that of the control rats. Isoproterenol stimulated insulin secretion more in the diabetic model than in the controls, and tolbutamide failed to evoke insulin secretion. Glucagon secretion in response to arginine and isoproterenol was similar in both groups, but was suppressed less efficiently be glucose in the model than in controls. Evidence for enhanced basal secretion of somatostatin was also found. Thus, these hyperglycemic rats have a selective defect in glucose-stimulated insulin secretion with preservation of responses to other agents. In addition, abnormalities in the secretion of glucagon and somatostatin have been found.

Animals↗
PubMed1980

A dual population of islets of Langerhans in bovine pancreas.

A morphological study of the bovine pancreas from fetus to adult documents the presence of two distinct types of pancreatic islets: large islets, 100 to 1600 micron in diameter, enmeshed in interlobular connective tissue; small islets, 25-200 micron in diameter, enmeshed in exocrine tissue. Large islets consisting primarily of well granulated B cells, decrease in relative volume with increasing age and in the adult are seldom seen. The overall relative volume of endocrine tissue is age dependent and ranges from 30% in the sixth month fetus to 10% in the neonate and 5% in the adult. Small islets contain B cells that increase their cytoplasmic secretory granularity with increasing fetal age, significantly degranulate just prior to birth and subsequently regranulate several weeks after birth. Beta cells of the small islets are uniquely characterized by junctional complexes in close association with large numbers of maculae adherentes (desmosomes). Using lanthanum-hydroxide and freeze-fracture techniques the junctional complexes are shown to consist of macula occludens (focal tight junctions) enclosing nexuses (gap junctions). The two types of islet differ in distribution, times of growth and times of B-cell granularity and may be indicative of functional differences yet to be elucidated.

Aging↗
PubMed1980

Nerve growth factor and pancreatic APUD cells.

Pancreatic endocrine cells have been considered APUD cells and been thought to be of neural crest origin. Neonatal rats were passively immunized with nerve growth factor antiserum and the development of neural crest derived superior cervical ganglia was markedly inhibited. The pancreatic content of glucagon, insulin, and somatostatin was unaffected, suggesting that pancreatic A,B, and D cells are under different developmental control than are cells of known neural crest origin.

APUD Cells↗