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Biomedical subjects

J R Gavin

Publications and source records attributed to J R Gavin.

At least 19 recordsLinked to original sources
PubMed2001

Pathophysiologic mechanisms of postprandial hyperglycemia.

The role of postprandial hyperglycemia in the etiology of diabetes-related complications and outcomes, although still being elucidated, is greater than previously thought. Acute glucose elevations after meal ingestion are associated with a variety of glucose-mediated tissue defects-oxidative stress, glycation, and advanced glycation end product formation-which have far-reaching structural and functional consequences for virtually every human organ system. Lowering glycosylated hemoglobin to levels that prevent or delay these complications can be achieved only by reducing both postprandial and fasting plasma glucose levels. The alpha-glucosidase inhibitors (acarbose, voglibose, miglitol) have been effective in delaying the digestion and absorption of carbohydrates, thus diminishing the postprandial surge in blood glucose levels without loss of calories. However, greater emphasis needs to be placed on the measurement of postprandial glycemia, so that readings can be used to guide treatment.

Humans↗
PubMed1998

New classification and diagnostic criteria for diabetes mellitus.

There has been an explosive growth in knowledge about diabetes mellitus since the National Diabetes Data Group promulgated diagnostic criteria and a classification system in 1979 that was largely adopted by the World Health Organization. However, recent findings regarding the levels of glucose associated with development of retinopathy, and growing confusion caused by a system of classification of diabetes based largely on the treatment used have led to a new assessment of the diagnosis and classification of diabetes mellitus. Using new data from population-based studies, and placing emphasis on a pathophysiology-based system of classification, in 1997, the Expert Committee of the American Diabetes Association released its recommendations for the classification and diagnosis of diabetes. The major changes from the 1979 report include: (a) the preferred use of the terms "type 1" and "type 2" instead of "insulin-dependent" and "non-insulin-dependent" to designate the two major types of diabetes mellitus; (b) a simplification of the diagnostic test to two fasting plasma glucose (FPG) determinations; and (c) a lower cutoff for FPG (126 mg/dL) to diagnose diabetes (this level of FPG having been found equivalent to the 200-mg/dL value in the oral glucose tolerance test for diagnosis). These changes provide an easier and more reliable means of diagnosing persons at risk of complications of hyperglycemia. Even though the fasting criterion was lowered, the total number of persons who will be diagnosed with diabetes by exclusive reliance on FPG will actually be somewhat less than with the old criteria. Moreover, epidemiologic data support the recommendation that screening for diabetes should start at age 45 and be repeated every 3 years in persons without risk factors, and earlier and more often in those with risk factors.

Biomarkers↗
PubMed1996

Diabetes in minorities: reflections on the medical dilemma and the healthcare crisis.

In summary, diabetes in minorities is clearly on the increase. The complication rates are likewise increasing, contributing to the large burden of health care costs. This is a significant medical dilemma inasmuch as these high-risk populations are among the fastest-growing segments of our society. Fortunately, delay and prevention of complications are now possible, although greater programmatic interventions will be required. The absence of such interventions is a reflection of the dimensions of our health care crisis. What is more, we have such poor insight into the reasons for the higher risks and rates of disease and its complications. This means that a critical step toward resolution of this dilemma is more research.

Black or African American↗
PubMed1995

An immunohistochemical and in situ hybridization study of insulin-like growth factor I within fetal neuron cell cultures.

Fetal neuron cell cultures (NCC) from 22 day gestation and 18 day gestation fetal rabbit brain were studied for the presence of insulin-like growth factor I (IGF I). The 22 day gestation NCC were incubated in an IGF I free/insulin free/serum free medium. The 18 day gestation NCC were incubated in: (1) IGF I free/insulin free/serum free medium, (2) IGF I containing medium (100 ng)/serum free medium, and (3) serum containing medium. The 22 day gestation NCC survived in the IGF I free/insulin free/serum free medium. Furthermore, IGF I was detected in the medium by RIA from day one to day ten of incubation. In contrast, the 18 day gestation NCC did not survive in the IGF I free/insulin free/serum medium, but survived in the serum medium. When the 18 day gestation NCC were incubated in the serum free medium containing 100 ng IGF I the cells survived for a period of 2-3 days. Immunoreactive IGF I was found within the 22 day gestation NCC incubated in the IGF I free/insulin free/serum free medium and 18 day gestation NCC in serum medium. Likewise, IGF I mRNA was found only within the 22 day gestation NCC. Internalization studies of IGF I have shown that the peptide was internalized from the medium by the two different gestational age NCC's studied. IGF I receptors were found in both 22 day gestation and 18 day gestation NCC. In conclusion IGF I may promote cell survival in early stages of brain development, and may be of exogenous origin. In contrast the 22 day gestation NCC are capable of producing and secreting IGF I, and indeed appear to respond to this growth factor in an autocrine fashion.

Animals↗
PubMed1995

Different genes for obesity are associated with insulin loss of regulation of the membrane (Ca2+ + Mg2+)-ATPase in the obesity syndrome. Lessons from animal models.

Intracellular Ca2+ homeostasis is impaired in tissues from obese humans and rats and insulin loses its regulatory effect on the plasma membrane (Ca2+ + Mg2+)-ATPase in kidney basolateral membranes (BLM) from the genetically obese fa/fa rats. We have demonstrated that loss of insulin regulation of the ATPase may impair insulin biologic effects and may therefore contribute to the insulin resistance in the obese rodents. To test whether the defect is restricted to one species or to one gene of obesity, studies were extended to an additional genetically obese rodent of another species the C57BL/6J ob/ob mice. Twelve-weeks-old obese and control male mice were used and (Ca2+ + Mg2+)-ATPase activity and its regulation by insulin were evaluated in their kidney BLM. The obese mice were heavier (56.4 +/- 2.5 vs 30.5 +/- 1.2 g P < 0.05), were hyperinsulinemic (6.32 +/- 1.87 vs 0.59 +/- 0.13 ng/ml P < 0.05) and had decreased (by 80%) specific binding of insulin to their epididymal fat cells compared with their non-obese littermates controls (ob/+, +/+). Yet, non-fasting plasma glucose levels were similar in the obese and control mice (227.0 +/- 19.3 vs 226.8 +/- 13.7 mg/dl N.S.). Basal activity of the (Ca2+ + Mg2+)-ATPase was similar in membranes from the ob/ob and control mice. However, while insulin (1-40 ng/ml) stimulated the ATPase activity in BLM form controls in a dose dependent manner (15-52%), no effect of insulin on the enzyme was seen in BLM from the obese mice even in the presence of the highest (40 ng/ml) concentration of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1994

Immunohistochemical and in situ hybridization study of an insulin-like substance in fetal neuron cell cultures.

We studied the ability of fetal neuron cell cultures from different rabbit fetal brain gestational ages to produce and secrete an insulin-like substance (ILS). Neurons from 22-day gestation were incubated in serum-containing medium or insulin-free/serum-free medium, and 18-day gestation fetal rabbit neurons were also incubated in serum-free/insulin containing medium and serum-containing medium. The 22-day cultures survived in the serum-containing medium and the insulin-free/serum-free medium. The 18-day cultures died when incubated in the insulin-free/serum-free or serum-free/insulin-containing medium, but survived when incubated in serum-containing medium. Using immunohistochemical and in situ hybridization techniques, ILS and insulin-like mRNA were demonstrated within the 22-day cultures incubated in all media compositions, but not within the 18-day cultures incubated in the serum-containing medium. Ultrastructural studies of the 22-day cultures demonstrated an ILS in the endoplasmic reticulum, Golgi and cytoplasm. Northern blots showed the presence of an insulin-like mRNA within the 22-day gestation neuron cell cultures. Insulin receptor was present in the 22-day cultures, but was absent in the 18-day cultures. In addition, we characterized the ILS from the 22-day cultures incubated in the insulin-free/serum-free medium employing high-performance liquid chromatography (HPLC), radioimmunoassay and Western blots. Analysis by HPLC and Western blots demonstrated the presence of an ILS in the extract. We have shown that while 22-day fetal neuron cultures produce and secrete an insulin-like substance indistinguishable from authentic insulin, neuron cell cultures from early brain development do not express this capability.

Animals↗
PubMed1994

Blood levels of insulin-like growth factors I and II in neonates of non-insulin-dependent diabetic rats.

Circulating levels of insulin like growth factor I (IGF-I) and insulin like growth factor II (IGF-II) were evaluated in plasma samples during the first 72 h of life in neonates of diabetic and control mother rats. Diabetes had been induced in the diabetic dams by streptozotocin at 2 days of age. The rats developed non-insulin dependent diabetes (at 6 weeks of age) and became pregnant at 11 weeks of age. Maternal blood glucose levels were higher in the diabetic mothers (P < 0.05) during the last two-thirds of gestation. Complications occurred at the end of 7.1% of the diabetic pregnancies but none of the controls. Analysis of neonates plasma glucose, IGF-I, and IGF-II concentrations in the first 12, 24, 48, and 72 h after birth revealed higher glucose levels in neonates of diabetic mothers at 72 h compared with controls (118 +/- 7 vs 85 +/- 5 mg/dl, P < 0.05) but there was no difference in IGF-I or IGF-II levels between the groups at any time point. Thus, acquired impaired glucose homeostasis may be seen in neonates of mildly diabetic mothers at early stages of their life but their circulating insulin-like growth factors levels are normal. These data do not support the proposition that fetal IGF-I and -II affect the outcome of pregnancies complicated by mild diabetes in the rodent.

Aging↗
PubMed1994

Diabetes mellitus: a disease of abnormal cellular calcium metabolism?

Although the pathogenesis of the diabetes mellitus syndrome remains poorly understood, both insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus predispose the individual to a similar spectrum of complications, including hypertension, macrovascular and microvascular disease, cataracts cardiomyopathy, neuropathy, and premature aging, suggesting that these complications develop along a pathway common to both diabetic conditions. Yet not all diabetic persons are affected by all of these complications or to the same degree. What causes this marked variability in the clinical manifestations of the diabetes syndrome remains an enigma. Accumulating data from animal models of diabetes and from studying patients with diabetes reveal that intracellular calcium levels are increased in most tissues. The activities of the membrane, adenosine triphosphatase (ATPase) associated cation pumps, which determine intracellular calcium level (i.e., calcium-ATPase and [sodium + potassium]-ATPase), are also altered. The nature of the alteration is often tissue specific and may depend on the level of blood glucose or insulin, or both. In this review we discuss the potential contribution of these changes in intracellular calcium regulation, whether acquired or genetically determined, to the pathogenesis of the diabetes syndrome, to the abnormalities in insulin secretion and action (mainly in non-insulin-dependent diabetes), and to the complications of both diabetes syndromes. Altered intracellular calcium metabolism may represent a common, underlying abnormality linking the metabolic, cardiovascular, ocular, and neural manifestations of the diabetic disease process.

Animals↗
PubMed1990

Effects of food restriction and insulin treatment on (Ca2+ + Mg2+)-ATPase response to insulin in kidney basolateral membranes of noninsulin-dependent diabetic rats.

Insulin increases (Ca2+ + Mg2+)-ATPase activity in cell membranes of normal rats but fails to do so in membranes of non-insulin-dependent diabetic (NIDD) rats. The loss of regulatory effect of the hormone on the enzyme might contribute to the insulin resistance observed in the NIDD animals. To further test this hypothesis, the effects of insulin treatment and acute food restriction on the ability of insulin to regulate the ATPase activity in kidney basolateral membranes (BLM) of NIDD rats were studied. Although insulin levels in NIDD and control rats were similar, plasma glucose was higher in the NIDD rats (18.3 +/- 1.5 v 19.3 +/- 1.7 microU/mL and 236 +/- 32 v 145 +/- 3 mg/dL, respectively). Insulin treatment (2 U/100 g), which increased plasma insulin in the NIDD rats (47.8 +/- 11.5 microU/mL; P less than .05), did not decrease their glucose (221 +/- 25 mg/dL). Higher insulin dose (4 U/100 g) decreased glucose level in the NIDD rats (73 +/- 3 mg/dL; P less than .001) but increased their plasma insulin 10-fold (202.5 +/- 52.5 microU/mL). Acute food restriction decreased glucose levels in the NIDD rats to levels seen in controls (135 +/- 3 mg/dL), while their insulin decreased by half (8.5 +/- 1.0 microU/mL; P less than .05). Basal (Ca2+ + Mg2+)-ATPase activity in BLM of all diabetic rats was higher than in controls (P less than .05). None of the treatments reversed this defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of insulin on glucose utilization in epitrochlearis muscle of rats with streptozocin-induced NIDDM.

Because skeletal muscle plays a major role in glucose disposal, it may be the primary site of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). Rates of glycogen synthesis (GS), glucose utilization via glycolysis, glycolytic utilization (GU), and glucose transport (GT) were studied in epitrochlearis muscles (EMs) obtained from 10-wk-old nonfasted Sprague-Dawley rats in which NIDDM was neonatally induced with streptozocin. Plasma glucose in NIDDM rats was elevated (P less than 0.001), whereas plasma insulin was similar in NIDDM and control rats. No differences in muscle weight, protein, glycogen, ATP, phosphocreatine, lactate, lactate-pyruvate ratios, or glucose-6-phosphate were noted in EMs of control and NIDDM rats. EMs were incubated in medium containing 5.6 or 11.2 mM glucose with tracer D-[5-3H]glucose and insulin from 0 to 7.18 x 10(-7) M for 1 or 2 h, and GS, GT, and GU were evaluated. Similar rates of basal (non-insulin-mediated) and insulin-stimulated GS, GU, and GT were observed in EMs of NIDDM and control rats incubated in 5.6 mM glucose for 2 h. Insulin dose-response curves revealed similar sensitivities and responsiveness. Increasing glucose concentration (from 5.6 to 11.2 mM) induced significant increases in basal rates of GS, GU, and GT in EMs of control but not NIDDM rats. Insulin dose-response curves for GS and GT revealed decreased sensitivity and no change in responsiveness in EMs of control and NIDDM rats, even though GU of EMs of NIDDM rats was significantly lower at basal and all other insulin concentrations. These data revealed that both insulin resistance and glucose resistance contribute to the impaired glucose metabolism in EMs of the NIDDM rat.

Adenosine Triphosphate↗
PubMed1989

Abnormal cell calcium concentrations in cultured bone cells obtained from femurs of obese and noninsulin-dependent diabetic rats.

Cytoplasmic free calcium concentration [Ca2+]i was quantified in cultured bone cells with osteoblastic characteristics. The cells were obtained from femurs of obese (fa/fa) Wistar-Kyoto rats, from nonobese, noninsulin-dependent diabetic (NIDD) Sprague Dawley rats, and from their appropriate controls. [Ca2+]i was also determined in bone cells obtained from in vivo insulin-treated NIDD rats. Obese (Wistar Kyoto) rats had increased body weight (313 +/- 13 vs. 249 +/- 4 g; P less than 0.01), decreased femur weights (0.68 +/- 0.05 vs. 0.89 +/- 0.05 g; P less than 0.05), similar glucose levels (148 +/- 5 vs. 139 +/- 3 mg/dl), and higher plasma insulin levels (6.0 +/- 0.5 vs. 0.7 +/- 0.1 ng/ml; P less than 0.01) when compared with their nonobese [(fa/+); (+/+)] littermates. Nonobese, NIDD rats, compared with their appropriate controls (nondiabetic Sprague Dawley rats) had higher plasma glucose levels (235 +/- 32 vs. 145 +/- 3 mg/dl; P less than 0.01) but their plasma insulins, body weights, and femur weights were similar to controls (0.7 +/- 0.1 vs. 0.6 +/- 0.1 ng/ml; 302 +/- 4 vs. 318 +/- 14 g; 0.97 +/- 0.4 vs. 0.98 +/- 0.04 g, respectively). Long-term (4 weeks) daily insulin treatment (2 u/100 g) of the NIDD rats increased their plasma insulin (1.9 ng/ml; P less than 0.05) and body weight (369 +/- 13 g; P less than 0.05) but did not change their plasma glucose levels (225 +/- 5 mg/dl), or femur weights (0.98 +/- 0.4 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Plasma membrane phospholipid content in non-insulin-dependent streptozotocin-diabetic rats--effect of insulin.

The activity of (Ca2+ +Mg2+)-ATPase is impaired in kidney basolateral membranes from non-insulin-dependent streptozotocin-diabetic rats. To study the possible role of changes in membrane phospholipid content in the malfunction of this enzyme in kidney membranes of the diabetic animals, phospholipid (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin) content was measured in kidney and liver membranes obtained from non-insulin-dependent diabetic rats. Total phospholipid content was similar in liver and kidney membranes of diabetic and control rats (595 +/- 47 versus 624 +/- 29 in liver and 469 +/- 22 versus 458 +/- 17 nmol Pi/mg protein in kidney respectively). Phosphatidylethanolamine content in kidney and liver membranes of diabetic rats was lower than in control rats (87.7 +/- 1.8 versus 96.4 +/- 2.2 nmol Pi/mg protein, p less than 0.01 and 87.1 +/- 3.7 versus 101.8 +/- 3.5, p less than 0.02 respectively). Phosphatidylinositol content was higher in kidney (28.0 +/- 0.6 versus 23.9 +/- 2.1, p less than 0.02) but not liver membranes from diabetic rats. The in vitro direct effect of insulin on the phospholipid content in kidney membranes was also measured. Physiologic concentrations of insulin (718 pmol/l for 30 min) increased the phosphatidic acid content in membranes from control but not from diabetic rats by 34.2% (p less than 0.02). This rise was readily measurable after 3 min of exposure to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Nutrition and somatomedin. XVI: Somatomedins and somatomedin inhibitors in fasted and refed rats.

Nutritional deprivation is associated with poor growth and decreased levels of net circulating somatomedin activity, as measured by bioassay. Since somatomedin activity reflects the contributions both of somatomedins (which stimulate cartilage) and of somatomedin inhibitors (which antagonize the ability of the somatomedins to stimulate cartilage), we asked if changes in net somatomedin activity could involve progressive underlying alterations in levels of both somatomedins and somatomedin inhibitors. Groups of rats were killed during three days of fasting and 24 hours of refeeding. Fasting was associated with a rise in serum beta-hydroxybutyrate from 1.6 to 12.6 mmol/L after one day, followed by a decline to 4 mmol/L at three days. Somatomedins (low-MW) were separated from somatomedin inhibitors (high-MW) by gel permeation chromatography at acid pH on Sephadex G-50 and TSK-2000 HPLC. Somatomedins fell 35% after one day of fasting, and decreased to 59% below control levels after three days (P less than .05). Somatomedins did not change with six hours of refeeding, but then rose rapidly, reaching control levels after 24 hours. Somatomedins were correlated with change in weight (r = .41, P less than .05), but not with glucose or beta-hydroxybutyrate. Inhibitors rose to 195% above control-levels after one day of fasting, and continued to rise to 375% above control after three days (P less than .01). In contrast to the delayed change in somatomedins with refeeding, there was an abrupt fall in inhibitors (41% below three-day fasted levels after six hours), returning to control levels after 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗