A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine.

Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once-daily subcutaneous injection for many people with diabetes, with a well-established efficacy and safety profile. New insulin glargine 300 units/ml (Gla-300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy.

Impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes treated with insulin glargine or NPH insulin.

AIM: To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin. METHODS: A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated. RESULTS: Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration. CONCLUSION: There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Optimum management of type 2 diabetes--timely introduction, optimization and intensification of basal insulin.

The natural progression of type 2 diabetes mellitus (T2DM) requires continuing medical care, early insulin intensification and patient self-management education to reduce the risk of long-term complications, including microvascular and macrovascular complications. However, too few people are on insulin, and all too commonly have poor glycaemic control. This paradigm significantly increases the risk for long-term complications. It is becoming increasingly apparent that the early introduction of basal insulin, such as insulin glargine, is essential to provide clinically important improvements in glycaemic control. In this review, we discuss the rationale for the earlier insulinization in T2DM in order to reach and maintain treatment targets and to provide further support for the recent American Diabetes Association and European Association for the Study of Diabetes consensus statement.

Beyond insulin replacement: addressing the additional needs of the diabetes patient.

The management of type 2 diabetes mellitus (T2DM) typically focuses on correcting dysglycaemia to reduce risk for microvascular and macrovascular complications, possibly by reducing glucose-mediated oxidative stress. However, other cardiometabolic risk factors, including abdominal obesity and dyslipidaemia are often overlooked in the quest for perfect glucose control. The currently used antidiabetic agents, including insulin, metformin, sulphonylureas and thiazolidinediones, have limited efficacy on these risk factors. A number of new therapeutic agents are undergoing clinical development, including glucagon-like peptide 1 mimetics (exenatide and liraglutide) and dipeptidyl peptidase 4 inhibitors (sitagliptin and vildagliptin), which target the incretin system, and the cannabinoid-1 receptor antagonists (rimonabant), which target the endocannabinoid system, may hold some promise for meeting these unmet needs. In this review, the clinical properties of these agents and potential treatment pathways to best use these agents are discussed for improving the management of T2DM and cardiovascular risk.

Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man.

To compare glutamine and alanine as gluconeogenic precursors, we simultaneously measured their systemic turnovers, clearances, and incorporation into plasma glucose, their skeletal muscle uptake and release, and the proportion of their appearance in plasma directly due to their release from protein in postabsorptive normal volunteers. We infused the volunteers with [U-14C] glutamine, [3-13C] alanine, [2H5] phenylalanine, and [6-3H] glucose to isotopic steady state and used the forearm balance technique. We found that glutamine appearance in plasma exceeded that of alanine (5.76 +/- 0.26 vs. 4.40 +/- 0.33 mumol.kg-1.min-1, P < 0.001), while alanine clearance exceeded glutamine clearance (14.7 +/- 1.3 vs. 9.3 +/- 0.8 ml.kg-1.min-1, P < 0.001). Glutamine appearance in plasma directly due to its release from protein was more than double that of alanine (2.45 +/- 0.25 vs. 1.16 +/- 0.12 mumol.kg-1.min-1, P < 0.001). Although overall carbon transfer to glucose from glutamine and alanine was comparable (3.53 +/- 0.24 vs 3.47 +/- 0.32 atoms.kg-1.min-1), nearly twice as much glucose carbon came from protein derived glutamine than alanine (1.48 +/- 0.15 vs 0.88 +/- 0.09 atoms.kg-1.min-1, P < 0.01). Finally, forearm muscle released more glutamine than alanine (0.88 +/- 0.05 vs 0.48 +/- 0.05 mumol.100 ml-1.min-1, P < 0.01). We conclude that in postabsorptive humans glutamine is quantitatively more important than alanine for transporting protein-derived carbon through plasma and adding these carbons to the glucose pool.

Glutamine and alanine metabolism in NIDDM.

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

Effect on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with T2DM.

AIMS: This study evaluated the effects on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with mild-to-moderate, but suboptimally controlled type 2 diabetes. METHODS: In this multicenter, double-blind, placebo-controlled study, 122 patients with type 2 diabetes inadequately controlled (A1c 7-8.5%) on metformin (> or =1000 mg/day for > or =3 months) were randomized to 16 weeks treatment with 2.5 mg/day glipizide GITS (n=61) or placebo (n=61), in addition to their current metformin dose. The primary efficacy variable was the change in A1c from baseline to endpoint. Changes in fasting plasma glucose (FPG), insulin concentrations, lipid profile and safety variables were also measured. RESULTS: The addition of glipizide GITS to metformin gave significantly greater improvements in mean A1c and FPG from baseline to endpoint than placebo addition (p<0.0002). Significantly more patients in the glipizide GITS group than in the placebo group achieved the target A1c level of A1c<7.0% (p<0.0001) and an A1c<6.5% (p<0.0033). Fasting insulin concentrations were similar in both groups and unchanged by treatment. Addition of glipizide GITS to metformin did not produce any significant or clinically relevant weight gain or changes in BMI. Both treatment regimens were well tolerated. CONCLUSIONS: This study showed that the addition of 2.5 mg glipizide GITS to metformin significantly improved glucose control in patients with type 2 diabetes inadequately controlled by metformin monotherapy.

Empagliflozin: a new treatment option for patients with type 2 diabetes mellitus.

Empagliflozin is an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by decreasing renal glucose reabsorption and promoting urinary glucose excretion. In clinical trials, empagliflozin demonstrated significant improvements in glycemic control, as monotherapy and in combination regimens. In addition, empagliflozin was associated with weight loss and moderate reductions in blood pressure. In the EMPA-REG OUTCOME study, empagliflozin significantly reduced the risk of the composite primary endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. Across the trials in general, empagliflozin was well tolerated, with no increased risk of hypoglycemia except when used with an insulin secretagogue or insulin. An increased risk of genital infections and urinary tract infections has been reported, although the association is less clear for urinary tract infections. Overall, empagliflozin appears to be a promising treatment for T2DM.

Do estrogens improve bone mineral density in osteoporotic women over age 65?

A retrospective analysis of our experience with estrogen and fluoride treatment in 91 patients with postmenopausal osteopenia followed for 6-47 months has been performed. Treatment included calcium (1000 mg/day) and either conjugated estrogens (0.625 mg/day) or sodium fluoride (50 mg/day), or both. All patients had at least two serial dual-photon spinal bone mineral density measurements performed 6 months or more apart. Estrogen treatment was associated with increased bone mineral density (5.3%/year), as was fluoride alone (7.5%/year). Estrogen and fluoride together were additive (9.6%/year). In women over age 65 the estrogen effect was just as great (6.9%/year) as in younger women. Estrogen benefit occurred predominantly in the first 18 months of treatment (7.0%/year), after which time changes in bone mineral density were similar to those in untreated controls, who showed stable bone mineral density. We conclude that aggressive estrogen and fluoride treatment tailored to the severity of the individual's postmenopausal osteopenia results in short-term improvement in spinal bone mineral density. These data further support that elderly women respond to estrogen replacement therapy with absolute and relative increments in bone density similar to those in younger women.

Homologous radioimmunoassay for human epidermal growth factor (urogastrone).

Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +/- 3.0 and 52.0 +/- 3.5 (mean +/- SE) micrograms/total vol, or 29.7 +/- 1.1 and 39.8 +/- 1.7 micrograms/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +/- 2.7 micrograms/g creatinine; P less than 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and beta-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +/- 2.6 micrograms/g creatinine) than normal men, but this was not significant (P greater than 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

Green fluorescent protein and its derivatives as versatile markers for gene expression in living Drosophila melanogaster, plant and mammalian cells.

We have investigated the utility of the green fluorescent protein (GFP) as a marker for gene expression in living adult Drosophila melanogaster (Dm) and cultured plant and mammalian cells. Using Dm, we generated transgenic flies bearing a glass-responsive gfp fusion gene to test the utility of GFP as a spatial reporter. In the adult living fly, GFP is clearly visible in the ocelli and the eye. We have optimized the use of filters for distinguishing the GFP signal from abundant autofluorescence in living Dm. In addition, we have used GFP to identify photoreceptor cells in pupal eye cultures that have been fixed and stained according to standard histological procedures. GFP was also detected in individual living plant cells following transient transfection of soybean suspension cultures, demonstrating that GFP is an effective transformation marker in plant cells. Similarly, transient transfection of mammalian cells with a modified form of GFP, S65T, allowed detection of single living cells expressing the reporter. This modified form of GFP gave a robust signal that was resistant to photobleaching. We then used a CellScan system exhaustive photon reassignment (EPR) deconvolution algorithm to generate high-resolution three-dimensional images of GFP fluorescence in the living cell.

The glycemic response to meals with six different fruits in insulin-dependent diabetics using a home blood-glucose monitoring system.

Glycemic effect of adding 10-g carbohydrate portions of apple, banana, grapes, honeydew, orange, or strawberries to a standard meal on separate occasions was measured in 10 insulin-dependent diabetics monitored at home. The meal comprised 29% of total daily caloric intake and contained green beans, rice, turkey, and margarine (50% carbohydrate, 20% protein, and 30% fat). Blood-glucose response to meals containing grapes, honeydew, orange, or strawberries was slightly higher than meals containing apple, banana, or no fruit and the small amount of starch in apple and banana may have contributed to their lower blood-glucose response compared to the other fruits tested. Age, duration of diabetes, or insulin regimen did not correlate with subjects' responses to fruit.

Bone demineralization, a factor of increasing significance in the management of primary hyperparathyroidism.

The significance of bone demineralization was evaluated for 97 patients treated surgically for primary hyperparathyroidism since 1980. Of 31 patients studied by bone densitometry, 16 showed moderate to severe osteoporosis. In approximately 20% of the total group, bone demineralization, including a bone fracture problem in some, was the dominant or a major indication for operation. Serial bone studies in six patients taken preoperatively or in patients not operated on for primary hyperparathyroidism showed an average loss of bone mineral density of 0.9% per year, whereas in four patients treated surgically serial studies showed an average increase of 9.8% per year. Although estrogen intake reduced serum calcium levels, significant bone demineralization or fractures were present in four patients aged 40 to 59 years and in five patients more than 60 years of age who had taken estrogens for many years. We conclude that in primary hyperparathyroidism, bone demineralization (1) justifies surgical correction in a significant number of patients; (2) should be evaluated, especially in elderly women; (3) is not prevented by estrogen intake, which may instead confuse decision making; (4) is reversed after surgical correction, but suggestions of incomplete reversal emphasize importance of this factor; (5) should be considered in postoperative management; and (6) involves many variables.

Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy.

The purpose of this study was to assess the effects of pulsatile intravenous insulin therapy (PIVIT) on the progression of diabetic nephropathy in patients with type 1 diabetes mellitus (DM). This 18-month multicenter, prospective, controlled study involved 49 type 1 DM patients with nephropathy who were following the Diabetes Control and Complications Trial (DCCT) intensive therapy (IT) regimen. Of these, 26 patients formed the control group (C), which continued on IT, while 23 patients formed the treatment group (T) and underwent, in addition to IT, weekly PIVIT. Blood pressure in all patients was maintained below 140/90 mm Hg on antihypertensive medication, preferentially using angiotensin-converting enzyme (ACE) inhibitors. All study patients were seen in the clinic weekly for 18 months, had monthly glycohemoglobin (HbA1c), and every 3 months, 24-hour urinary protein excretion and creatinine clearance (CrCl) determinations. The HbA1c levels declined from 8.61% +/- 0.33% to 7.68% +/- 0.31% (P = .0028) in the T group and from 9.13% +/- 0.36% to 8.19% +/- 0.33% (P = .0015) in the C group during the study period. CrCl declined significantly in both groups, as expected, but the rate of CrCl decline in the T group (2.21 +/- 1.62 mL/min/yr) was significantly less than in the C group (7.69 +/- 1.88 mL/min/yr, P = .0343). We conclude that when PIVIT is added to IT in type 1 DM patients with overt nephropathy, it appears to markedly reduce the progression of diabetic nephropathy. The effect appears independent of ACE inhibitor therapy, blood pressure, or glycemic control.

Avoiding reoperation for indeterminate thyroid nodules identified as malignant after surgery.

Thyroid nodules that are indeterminate as carcinoma by needle biopsy before surgery and by study of frozen sections at the time of surgery are occasionally identified to be malignant in later studies. If only a lobectomy has been performed, the advisability of reoperation to remove the remaining thyroid tissue to facilitate radioactive iodine therapy may cause concern. To obviate this difficulty as well as to reduce the occurrence of nodules later in a preserved contralateral thyroid lobe and to provide additional thyroid tissue for study, contralateral subtotal or near total lobectomy has been performed for indeterminate thyroid nodules. The small remnant of remaining thyroid tissue can later be ablated by radioactive iodine if desired. Of 37 patients with indeterminate thyroid nodules, none required reoperation, although the diagnosis of carcinoma was established after surgery for eight patients, three of whom were treated with radioactive iodine.

Repaglinide in type 2 diabetes: a 24-week, fixed-dose efficacy and safety study.

In this 24-week multicenter, double-blind, randomized, fixed-dose trial, 361 patients having type 2 diabetes received daily preprandial treatment with placebo (n = 75), repaglinide 1 mg (n = 140), or repaglinide 4 mg (n = 146). By a last-observation carried-forward calculation, repaglinide 1 mg or 4 mg treatment decreased mean fasting plasma glucose (FPG) values (by -47 mg/dL or -49 mg/dL) while the placebo group had increased FPG values (by 19 mg/dL). For the repaglinide treatment groups at the end of the study, changes in HbA1c from baseline values ranged from 1.8 to 1.9 percentage points lower than the placebo group. There were no events of severe hypoglycemia. Nearly all hypoglycemic symptom episodes had blood glucose levels above 45 mg/dL. Repaglinide was well tolerated in a preprandial fixed-dose regimen of 1 mg or 4 mg, assigned without adjustment for clinical parameters.

Patient compliance and persistence with antihyperglycemic drug regimens: evaluation of a medicaid patient population with type 2 diabetes mellitus.

BACKGROUND: Drug use patterns among patients with type 2 diabetes mellitus have been studied in the general population but not specifically in the Medicaid population. OBJECTIVE: The purpose of this study was to examine antihyperglycemic drug use patterns among Medicaid recipients with type 2 diabetes and assess patients' persistence and compliance with different antihyperglycemic drug regimens. METHODS: Pharmaceutical claims data from Medi-Cal for January 1996 through September 1998 were analyzed to investigate antihyperglycemic drug use patterns over a 1-year and 2-year period. Prescription refill data were examined to assess patient compliance and persistence. RESULTS: Of the 37,431 patients in the 1-year follow-up cohort, 79.6% started antihyperglycemic treatment with monotherapy (ie, drug therapy with a single class of antihyperglycemic medication), 14.5% with insulin alone, 3.9% with polytherapy (ie, drug therapy with > or = 2 classes of medication other than insulin), and 2.1% with insulin plus another therapy. Of the patients receiving monotherapy, 85.3% were taking a sulfonylurea, 14.0% were taking metformin, and 0.7% were taking another agent. In the 1-year follow-up, 55.5% of patients taking metformin alone, 67.2% of those taking sulfonylurea alone, and 83.9% of those taking metformin plus sulfonylurea (M + S) did not undergo any modification of their regimen (except discontinuation of therapy). Among these patients, those taking metformin or sulfonylurea alone had approximately 65% more days of continuous (or persistent) treatment (129 and 128 days, respectively) per patient per year than did patients taking polytherapy (78 days). In addition, sulfonylurea or metformin monotherapy was associated with a 36% higher compliance rate than M + S polytherapy (177 days vs 130 days). CONCLUSION: Simple 1-drug antihyperglycemic regimens were associated with better compliance and persistence (as measured by prescription refill data) than more complex multiple-drug regimens among patients with type 2 diabetes in the Medi-Cal population.

Thyroid nodules indeterminate by needle biopsy.

In our experience with 121 patients 18 (15 percent) thyroid nodules studied by needle biopsy were considered indeterminate relative to the presence of a low-grade, well-differentiated carcinoma. For 11 of the 18 patients, operation was performed with carcinoma identified in two (18 percent). Although experience reduced this problem, the frequency of carcinoma justifies operation for patients with indeterminate thyroid nodules by needle biopsy, unless other factors dictate otherwise. Inadequate results of fine-needle aspiration biopsy requires a determination of therapy on the basis of other clinical factors. However, permanent disappearance or great reduction in size following aspiration of cystic nodules, repeat biopsy, and biopsy with large needles are important in supporting nonoperative therapy. The indeterminate and inadequate cases must be considered in assessing reports of the use of needle biopsy of thyroid nodules. The large size of a thyroid nodule and previous external radiation therapy are factors supporting operative treatment. Improved selection of patients with benign thyroid nodules for thyroid hormone suppression therapy is needed--thyroid-releasing hormone testing may be of help.

Patient compliance and persistence with anti-hyperglycemic therapy: evaluation of a population of type 2 diabetic patients.

The persistence and compliance of type 2 diabetic patients to different regimens of anti-hyperglycemic therapy were assessed retrospectively. The pharmacy claims from a pharmacy benefit management organization were analysed from the third quarter of 1996 to the fourth quarter of 1999. Of the 23,400 patients enrolled and initiating anti-diabetic therapy, 85% started treatment with monotherapy, 9.5% with insulin alone, 4.1% with polytherapy and 1.3% with insulin plus another therapy. Monotherapy patients were characterized as receiving metformin, sulfonylurea or another agent. For the 1-year follow-up period, 70.5% of the metformin patients, 75.3% of the sulfonylurea patients and 86.8% of the polytherapy patients underwent no regimen modification (except discontinuation). For the patients who had no modification of their medication regimen, persistence with sulfonylurea or metformin monotherapy was 65% greater than with polytherapy over a 1-year period. Compliance with sulfonylurea or metformin monotherapy was 45% greater than with polytherapy.

Novel Jun- and Fos-related proteins in Drosophila are functionally homologous to enhancer factor AP-1.

A homolog of mammalian enhancer binding factor AP-1 was detected in Drosophila and was purified from embryo nuclear extracts by sequence-specific DNA affinity chromatography. The purified fraction, dAP-1, displays the sequence specificity as well as transcriptional activation properties of mammalian AP-1 and consists of two major proteins of mol. wts 40 and 70 kd. Antibody cross-reactivity experiments suggest that these proteins are Drosophila homologs of proto-oncogene products, Jun and Fos. The Drosophila Jun- and Fos-related antigens, when separated, are individually capable of sequence-specific DNA binding, and the Jun-related antigen activates transcription in vitro.