bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method for Large-Scale Isolation of Pancreatic Islets by Tissue Culture of Fetal Rat Pancreas
Authors: Hellerström Claes , Lewis Nancy Jo , Borg Håkan , Johnson Robert , Freinkel Norbert 
Published: September 2013

Detailed studies of the maturation of stimulus-secretion coupling of the pancreatic B-cell requires a supply of isolated fetal islets, which has so far been difficult to obtain. To overcome this problem we have maintained minced and mildly collagenase-digested fetal rat pancreatic glands (21.5 days gestational age) in tissue culture to enable degeneration of the acinar part, leaving the endocrine cells in an isolated and surviving state. Indeed, after 1 wk in culture there was a complete separation between acinar and endocrine cells with the appearance of numerous discrete islets and the disappearance or dedifferentiation of the exocrine cells. Isolated islets were either free floating or attached on top of a monolayer of fibroblast-like cells. Their number after 1 wk in culture was estimated as about 90 per explanted fetal pancreas and a total yield of about 5000 isolated islets was easily achieved. Both light arid electron microscopic examinations showed an excellent structural preservation with a marked predominance of well-granulated B-cells. Numerous islets of the same weight as that measured in cultured islets of adult rats were regularly found after 1 wk in culture. The insulin concentration of the cultured fetal islets was related to the glucose concentration of the growth medium. A similar relationship was found with respect to the insulin release in response to glucose. Thus, fetal islets cultured for 8 days in growth media containing 11.1 or 22.2 mM glucose showed a marked and significant insulin response to glucose in batch-type incubations at the end of the culture period. By contrast, the glucose stimulation of insulin release was insignificant in islets cultured at 5.5 or 2.8 mM glucose. When the culture period was confined to 1 day, there were no effects of glucose on the insulin release irrespective of the glucose concentration of the growth medium.
It is concluded that the present technique for tissue culture of fetal rat pancreas makes it possible to isolate substantial amounts of fetal islets predominantly composed of B-cells. The transition in vitro from a poor glucose sensitivity to an adult-type insulin response indicates that the technique can be used in further detailed studies of the molecular mechanisms involved in the growth and development of the pancreatic B-cell.
Effect of Diet-induced Obesity on Glucose and Insulin Tolerance of a Rodent with a Low Insulin Response (Acomys cahirinus)
Authors: Gutzeit Arndt , Renold Albert E , Cerasi Erol , Shafrir Eleazar 
Published: September 2013

Spiny mice (Acomys cahirinus) from the Geneva colony tend to develop diabetes, whereas those maintained in Jerusalem do not. The role of environmental factors in the development of glucose intolerance was investigated by diet exchanges in specimens from the two colonies. Spiny mice on the Geneva diet (laboratory chow supplemented by a seed mixture containing 15% fat by weight) developed massive obesity over 8–10 months; body lipid content increased threefold compared with albino mice and was twofold higher than in spiny mice maintained on the laboratory chow in Jerusalem or in spiny mice living in their natural habitat near the Dead Sea. Spiny mice from the Geneva colony, kept on the laboratory chow alone, were as lean as animals from the Jerusalem colony. Similarly, Jerusalem Acomys given pellets supplemented by seeds developed marked obesity. Liver and adipose tissue enzymes in spiny mice transferred to the seed-supplemented diet showed adaptation typical for fat feeding: decrease in the capacity of glycolysis, NADPH generation, and fatty acid synthesis.
The obesity was associated with insulin resistance, evident from a negative correlation between the extent of hypoglycemia after i.v. insulin administration and body lipid content. The glucose disappearance rate (K value) was significantly reduced by obesity, but the insulin response to i.v. glucose increased only moderately. In all the Acomys groups studied, insulin response to i.v. glucose was markedly lower in comparison with the response in albino mice.
The following conclusions are drawn: (1) Low insulin response to glucose is a species-characteristic of spiny mice whether the animals are bred in laboratories or live in freedom. (2) Given an appropriate diet, spiny mice develop obesity, accompanied by pronounced insulin resistance. (3) Obesity may be one of the causes of the marked islet hyperplasia in laboratory-kept spiny mice, but this does not result in increased insulin output. (4) The inability of spiny mice to respond with augmented insulin secretion when insulin efficiency is reduced may be responsible for the accelerated development of glucose intolerance in this species. Thus, the liability of Geneva spiny mice to develop diabetes may be caused by the obesity-inducing diet used in this colony rather than to a specific genetic characteristic. (5) The fact that insulin resistance in spiny mice occurs without the development of hyperinsulinemia suggests that similar mechanisms may operate in the development of glucose intolerance in human, low, insulin responders.
Somatostatin Concentration Responds to Arginine in Portal Plasma: Effects of Fasting, Streptozotocin Diabetes, and Insulin Administration in Diabetic Rats
Authors: Kazumi Tsutomu , Utsumi Masafumi , Yoshino Gen , Ishihara Kazuhide , Hirose Yoshikazu , Makimura Hiroyuki , Baba Shigeaki 
Published: September 2013

Changes of somatostatin concentration in response to a single i.v. injection of arginine (400 mg/kg body weight) were examined in extracted portal plasma of normal and diabetic rats in the fully fed state and after 24 h of fasting, as well as in diabetic rats treated with insulin for one week. In both normal and diabetic animals fasted for 24 h, the basal level of somatostatin declined but the magnitude of the arginine-induced elevation of somatostatin was not affected, suggesting a physiologic role of the tetradecapeptide in nutrient homeostasis.
When compared with intact rats, diabetic animals were shown to have increased levels of somatostatin before and after arginine administration, both of which were attenuated by insulin replacement therapy. These findings suggest that alterations of D cell function in streptozotocin diabetes may be related to either insulin deficiency or its metabolic consequences.
Transplantation of Dispersed Pancreatic Islet Tissue in Humans: Autografs and Allografts
Authors: Sutherland David E R , Matas Arthur J , Goetz Frederick C , Najarian John S 
Published: September 2013

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (&gt;97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral feedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr.
Seven diabetic renal eliografi recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function —increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements— occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.
Development of Adipose Tissue in Newborns of Gestational-diabetic and Insulin-dependent Diabetic Mothers
Authors: Enzi G , Inelmen E M , Caretta F , Villani F , Zanardo V , DeBiasi F 
Published: September 2013

Some parameters of adipose tissue development have been studied in normal, full-term infants of gestational-diabetic mothers (GDM) and insulin-dependent diabetic mothers (IDDM). Values of skinfold thickness, body fat mass, and fat cell weight in full-term newborns of GDM and IDDM are greater than in infants of nondiabetic mothers. Fat mass enlargement in newborns of diabetic mothers seems to be caused almost exclusively by an increase in the triglyceride content of the single adipocytes. Results of determinations of fat cell weight are in fact significantly higher in newborns of GDM and IDDM and correlate closely with skinfold thickness and body fat mass: No differences resulted in the approximate estimate of fat cell number. Neither maternal weight gain during pregnancy nor pregravidic overweight seem to be directly related to the expansion of adipose tissue observed in newborns of diabetic mothers. Maternal blood glucose levels and neonatal IRI levels in cord blood significantly correlated with fat cell weight. Maternal FFA levels are not related to parameters of adipose tissue development in newborns of normal, GD, and IDD mothers.
In conclusion, enlargement of body fat mass in full-term infants of GDM and IDDM is dependent on glucose availability and, thus, on the insulin-induced enhancement of triglyceride synthesis and storage in single adipocytes. Free fatty acids do not seem to play an important role in regulating the triglyceride content of fat cells in newborns of gestational-diabetic or insulin-dependent diabetic mothers.
A Decreased Response of Cyclic Adenosine Monophosphate Concentrations to Glucagon in Liver Slices from Streptozotocin-induced Diabetic Rats
Authors: Yamashita Kamejiro , Yamashita Somo , Yasuda Hiroko , Oka Yuji , Ogata Etsuro 
Published: September 2013

Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 μg/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups.
Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats.
Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats.
These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known.
HbA1 in Subjects with Abnormal Glucose Tolerance but Normal Fasting Plasma Glucose
Authors: Bolli Geremia , Compagnucci Pietro , Cartechini Maria G , Santeusanio Fausto , Cirotto Carlo , Scionti Luciano , Brunetti Paolo 
Published: September 2013

HbA1(a+b+c)(HbA1) was determined chromatographically in 107 subjects with normal fasting plasma glucose (FPG) and 112 patients with overt diabetes. Subjects with normal FPG were divided into two groups based on their response to two oral glucose tolerance tests (OGTTs), at an interval of 2 mo. In 40 subjects with normal OGTT (group I), HbA1 ranged from 5.2% to 7.2%, while in 67 subjects with abnormal OGTT (group II), it ranged from 6.3% to 9.6%. HbA1 levels were significantly higher in group II than in group I (7.7 ± 0.09% versus 6.4 ± 0.08%, mean ± SEM, P &lt; 0.0005), but 14 subjects of group II had HbA1 levels less than 7.2%. No correlation was found between HbA1 and FPG, OGTT peak, and curve area in either group. However, the correlation became significant in all 107 subjects with normal FPG (groups I + II). In patients with overt diabetes, HbA1 ranged from 6.3% to 18% (11.9 ± 0.22%) and correlated with FPG (r = 0.78, P &lt; 0.0005).
The traditional OGTT seems more sensitive than the HbA1 measurement in detecting subjects with reduced carbohydrate tolerance. HbA1 level, on the other hand, is known to be a more specific indicator of structural abnormalities following long-term hyperglycemia. Thus HbA1 determination might be a helpful test along with OGTT to improve both selection and follow-up of subjects with true borderline diabetes.
Effect of Adrenergic Agents on the Secretion of Gastrointestinal Immunoreactive Glucagon in Depancreatized Dogs
Authors: Yoshida Toshihide , Kondo Motoharu 
Published: September 2013

To elucidate the mode of action of adrenergic agents on gastric A cells, the effects of infusion of adrenergic agonists and antagonists on the secretion of gastrointestinal immunoreactive glucagon (gastrointestinal IRG) from gastric A cells were investigated in 45 conscious, depancreatized dogs untreated with insulin.
Large amounts (0.6 μg/kg/min) of epinephrine, norepinephrine, and isoproterenol stimulated the release of gastrointestinal (RG, and catecholamine-induced gastrointestinal IRG release was completely abolished by simultaneous infusion of the specific beta receptor-blocking compound, propranolol, but not by alpha receptor blockade with phentolamine.
These findings suggest that, when adrenergic agonists are infused in large amounts, they may act through a beta receptor to increase the release of gastrointestinal IRG.
Acute Changes in Brain Tryptophan and Serotonin After Carbohydrate or Protein Ingestion by Diabetic Rats
Authors: Crandall Elizabeth A , Fernstrom John D 
Published: September 2013

In normal, fasting rats, intubation with glucose did not alter serum tryptophan, but it did reduce serum concentrations of the large neutral amino acids, tryptophan's competitors for brain uptake. The serum ratio of tryptophan to the sum of these competitors, which predicts brain tryptophan uptake, was thus increased. Brain tryptophan, serotonin (which is synthesized from tryptophan), and 5-hydroxyindoleacetic acid levels also increased. Such increases in brain serotonin are potentially important, since serotonin is a neurotransmitter. Changes in its level may indicate altered release by neurons and, thus, modified brain function. In contrast, glucose intubation of fasting streptozotocindiabetic rats elicited only a small increase in the serum tryptophan ratio. Brain tryptophan increased slightly; no changes occurred in brain serotonin or in 5-hydroxyindoleacetic acid. Similar effects were noted when fasting diabetic rats consumed a single, carbohydrate meal. However, brain indoles did increase after carbohydrate ingestion in diabetic rats that received an insulin injection at the time food was presented.
Effects of ingesting a protein-containing meal were also studied. In normal rats, consumption of this meal increased the serum tryptophan ratio slightly. Brain tryptophan and serotonin levels were unchanged. In diabetic rats, ingestion of the protein-containing meal often lowered the serum tryptophan ratio. Brain tryptophan also fell in diabetic rats when the serum tryptophan ratio was reduced, but brain 5-hydroxyindoles did not fall.
The data demonstrate that the absence of a carbohydrate-induced increment in brain indole levels follows indirectly from the absence of the insulin-induced rise in the serum tryptophan ratio. The diabetic rat's inability to experience normal carbohydrate-induced increments in brain serotonin suggests that brain functions, normally dependent on such neurochemical signals, may be abnormal.
Critical Factors in the Chromatographic Measurement of Glycohemoglobin (HbA1)
Authors: Simon M , Eissler J 
Published: September 2013

Measurement of glycohemoglobin has been proposed as a criterion for the management of diabetes mellitus. We evaluated various conditions critical to the accuracy and precision of the cation-exchange method.
Tolerance limits for each variable were defined as follows: phosphate-eluding buffer (0.06 ± 0.005 mol/L ph 6.70−6.72), column temperature (19−21°C), and resin equilibration (to phosphate buffer, 0.07 mol/L, pH 6.70 ± 0.01). Hemoglobin absorbance measured in the Sorét region (approximately 416 nm) of the first chromatographic fraction divided by that of the total hemolysate provided the most accurate and precise result. Overall between-run precision expressed as coefficient of variation (CV, in percent) of normal and diabetic pools was 4.8% and 5.1%, respectively. When purified HbA1c was added to hemolysates, recovery was 90–95%. Results were linear to at least 18% glycohemoglobin. Hemoglobin F (HbF) interfered with the method, whereas HbC and HbS did not. Red cells could be stored frozen for at least 6 days, thus easing transport of outpatient samples. A reference range of 6.0−8.8% glycohemoglobin was established from 85 nondiabetic adults (ages 23–65 yr). In a clinical study, only 4 of 13 treated diabetic patients believed to be in good control showed glycohemoglobin results within the normal range. All of the 19 treated diabetics in fair or poor control showed glycohemoglobin results greater than 10% of total Hb, ie., well above the normal range.
Islet Cell and Other Organ-specific Antibodies in U.S. Caucasians and Blacks with Insulin-dependent Diabetes Mellitus
Authors: Neufeld Michel , Maclaren Noel K , Riley William J , Lezotte Dennis , McLaughlin Judith V , Silverstein Janet , Rosenbloom Arlan L 
Published: September 2013

SUMMARY
Islet cell antibodies (ICA) were detected in 168 (33%) of 504 patients with insulin-dependent diabetes mellitus (IDDM). Mean age of onset of IDDM was 8.6 ± 0.2 yr and mean age at testing was 13.4 ± 0.3 yr. None of 162 controls without diabetes (mean age 21.8 ± 0.9 yr) had ICA. Caucasian patients (404) had a 74% frequency of ICA within 3 mo of diagnosis and an overall ICA frequency of 36%. These results were similar to those reported from Europe. Black patients (100) had lower frequencies of ICA (P &lt; 0.01) and thyroid antibodies (P &lt; 0.05). Caucasian patients with onset of IDDM before 5 yr of age (107) had a lower frequency (P &lt; 0.01) of ICA (21%) than those (297) with a later age of onset (42%). Patients with persistent ICA beyond 5 yr of IDDM had increased frequencies of gastric parietal and adrenal cortex cell antibodies. Thyroid microsomal antibodies were less frequent (P &lt; 0.05) in blacks (4%) than in Caucasians (20%). The former did not have adrenal antibodies. Similar ICA frequencies among Caucasians with IDDM in the U.S. and in Europe suggest that etiologie factors are similar in the two geographic regions. The lower frequencies of ICA in patients with IDDM onset before 5 yr of age suggest that some of these patients may have a different etiology and/or a more rapid disappearance of islet cell antigens than patients with a later onset. The lower ICA frequencies in black patients can be explained by heterogeneity of IDDM in this group and by admixture of IDDM susceptibility genes from the Caucasian genome to the black genome.
The Prevalence of Diabetes in the Rural and Urban Polynesian Population of Western Samoa
Authors: Zimmet P , Faaiuso S , Ainuu J , Whitehouse S , Milne B , Deboer W 
Published: September 2013

Rural-urban comparisons of diabetes prevalence were made in the Polynesian population of Western Samoa. The prevalence of diabetes in the urban population was almost three times that in the rural (10.1% versus 3.6%).
While the urban male and female subjects were significantly more obese than their rural counterparts, the difference in prevalence rate could not be wholly explained on this basis. Diabetes prevalence was still approximately double in urban subjects when we compared the rural and urban populations after removing the differences in obesity and age. The results suggest that, apart from age and obesity, other factors, e.g., differences in diet, physical activity, or stress (or a combination of these), may participate in the rural to urban difference in diabetes prevalence.
Responses of Neonatal Rat Islets to Streptozotocin: Limited B-Cell Regeneration and Hyperglycemia
Authors: Bonner-Weir S , Trent D F , Honey R N , Weir G C 
Published: September 2013

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 ± 8 mg/dl versus control (C), 127 ± 2) that was associated with a marked reduction of B-cell numbers (SZ, 26.5 ± 2.6% B-cell per islet versus C, 72.8 ± 0.8%). By 10 days of age the SZ animals became normoglycemic with partial recovery of the B-cell number (SZ, 39.6 ± 2.1% versus C, 64.0 ± 2.6%). By 6 weeks hyperglycemia returned (SZ, 345 ± 5.2 mg/dl versus C, 171 ± 6.2) with B-cell number of the SZ being 72% of the C (SZ, 48.8 ± 2.4% versus C, 67.5 ± 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 an 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-celle 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.